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Monoclonal antibodies are highly valuable tools in biomedicine but the generation by hybridoma technology is very time-consuming and elaborate. In order to circumvent the consisting drawbacks an in vitro immunization approach was established by which murine as well as human monoclonal antibodies against a viral coat protein could be developed. The in vitro immunization process was performed by isolation of murine hematopoietic stem cells or human monocytes and an in vitro differentiation into immature dendritic cells. After antigen loading the cells were co-cultivated with naive T and B lymphocytes for three days in order to obtain antigen-specific B lymphocytes in culture, followed by fusion with murine myeloma cells or human/murine heteromyeloma cells. Antigen-specific hybridomas were selected and the generated antibodies were purified and characterized in this study by ELISA, western blot, gene sequencing, affinity measurements. Further the characteristics were compared to a monoclonal antibody against the same target generated by conventional hybridoma technology. Isotype detection revealed a murine IgM and a human IgG4 antibody in comparison to an IgG1 for the conventionally generated antibody. The antibodies derived from in vitro immunization showed indeed a lower affinity for the antigen as compared to the conventionally generated one, which is probably based on the significantly shorter B cell maturation (3 days) during the immunization process. Nevertheless, they were suitable for building up a sandwich based detection system. Therefore, the in vitro immunization approach seems to be a good and particularly fast alternative to conventional hybridoma technology.
Pancreatic secretory zymogen-granule membrane glycoprotein 2 (GP2) has been identified to be a major autoantigenic target in Crohn’s disease patients. It was discussed recently that a long and a short isoform of GP2 exists whereas the short isoform is often detected by GP2-specific autoantibodies. In the outcome of inflammatory bowel diseases, these GP2-specific autoantibodies are discussed as new serological markers for diagnosis and therapeutic monitoring. To investigate this further, camelid nanobodies were generated by phage display and selected against the short isoform of GP2 in order to isolate specific tools for the discrimination of both isoforms. Nanobodies are single domain antibodies derived from camelid heavy chain only antibodies and characterized by a high stability and solubility. The selected candidates were expressed, purified and validated regarding their binding properties in different enzyme-linked immunosorbent assays formats, immunofluorescence, immunohistochemistry and surface plasmon resonance spectroscopy. Four different nanobodies could be selected whereof three recognize the short isoform of GP2 very specifically and one nanobody showed a high binding capacity for both isoforms. The KD values measured for all nanobodies were between 1.3 nM and 2.3 pM indicating highly specific binders suitable for the application as diagnostic tool in inflammatory bowel disease.
Twenty-four scientists met at Aschauhof, Altenhof, Germany, to discuss the associations between child growth and development, and nutrition, health, environment and psychology. Meta-analyses of body height, height variability and household inequality, in historic and modern growth studies published since 1794, highlighting the enormously flexible patterns of child and adolescent height and weight increments throughout history which do not only depend on genetics, prenatal development, nutrition, health, and economic circumstances, but reflect social interactions. A Quality of Life in Short Stature Youth Questionnaire was presented to cross-culturally assess health-related quality of life in children. Changes of child body proportions in recent history, the relation between height and longevity in historic Dutch samples and also measures of body height in skeletal remains belonged to the topics of this meeting. Bayesian approaches and Monte Carlo simulations offer new statistical tools for the study of human growth.
The origin of ambling horses
(2016)
Horseback riding is the most fundamental use of domestic horses and has had a huge influence on the development of human societies for millennia. Over time, riding techniques and the style of riding improved. Therefore, horses with the ability to perform comfortable gaits (e.g. ambling or pacing), so-called ‘gaited’ horses, have been highly valued by humans, especially for long distance travel. Recently, the causative mutation for gaitedness in horses has been linked to a substitution causing a premature stop codon in the DMRT3 gene (DMRT3_Ser301STOP) [1]. In mice, Dmrt3 is expressed in spinal cord interneurons and plays an important role in the development of limb movement coordination [1]. Genotyping the position in 4396 modern horses from 141 breeds revealed that nowadays the mutated allele is distributed worldwide with an especially high frequency in gaited horses and breeds used for harness racing [2]. Here, we examine historic horse remains for the DMRT3 SNP, tracking the origin of gaitedness to Medieval England between 850 and 900 AD. The presence of the corresponding allele in Icelandic horses (9th–11th century) strongly suggests that ambling horses were brought from the British Isles to Iceland by Norse people. Considering the high frequency of the ambling allele in early Icelandic horses, we believe that Norse settlers selected for this comfortable mode of horse riding soon after arrival. The absence of the allele in samples from continental Europe (including Scandinavia) at this time implies that ambling horses may have spread from Iceland and maybe also the British Isles across the continent at a later date.
Adsorption of amino acids on the magnetite-(111)-surface: a force field study (vol 19, 851, 2013)
(2016)
Communicative Reason Juergen Habermas, interviewed by Christoph Demmerling and Hans-Peter Krueger
(2016)
Jurgen Habermas explicates the concept of communicative reason. He explains the key assumptions of the philosophy of language and social theory associated with this concept. Also discussed is the category of life-world and the role of the body-mind difference for the consciousness of exclusivity in our access to subjective experience. as well as the role of emotions and perceptions in the context of a theory of communicative action. The question of the redemption of the various validity claims as they are associated with the performance of speech acts is related to processes of social learning and to the role of negative experiences. Finally the interview deals with the relationship between religion and reason and the importance of religion in modern, post-secular societies. Questions about the philosophical culture of our present times are discussed at the end of the conversation.
In this Comment, we review the results of pattern formation in a reaction-diffusion-advection system following the kinetics of the Gray-Scott model. A recent paper by Das [Phys. Rev. E 92, 052914 (2015)] shows that spatiotemporal chaos of the intermittency type can disappear as the advective flow is increased. This study, however, refers to a single point in the space of kinetic parameters of the original Gray-Scott model. Here we show that the wealth of patterns increases substantially as some of these parameters are changed. In addition to spatiotemporal intermittency, defect-mediated turbulence can also be found. In all cases, however, the chaotic behavior is seen to disappear as the advective flow is increased, following a scenario similar to what was reported in our earlier work [I. Berenstein and C. Beta, Phys. Rev. E 86, 056205 (2012)] as well as by Das. We also point out that a similar phenomenon can be found in other reaction-diffusion-advection models, such as the Oregonator model for the Belousov-Zhabotinsky reaction under flow conditions.
The Gradient Symbolic Computation (GSC) model presented in the keynote article (Goldrick, Putnam & Schwarz) constitutes a significant theoretical development, not only as a model of bilingual code-mixing, but also as a general framework that brings together symbolic grammars and graded representations. The authors are to be commended for successfully integrating a theory of grammatical knowledge with the voluminous research on lexical co-activation in bilinguals. It is, however, unfortunate that a certain conception of bilingualism was inherited from this latter research tradition, one in which the contrast between native and non-native language takes a back seat.
It is argued that, despite differences in cultural norms and practices, the evidence for a link between violent media use and aggression is remarkably consistent across different countries. Along with evidence that different operationalizations of violent media use also converge across countries, these findings strengthen the conclusion that violent media are a risk factor for aggression and validate the psychological explanations for these effects. However, we need comparative studies based on a consistent methodology and a theory-based selection of cultural difference variables to properly examine the potential impact of culture on the association between violent media use and aggression.
Ius emigrandi
(2019)
Reply to Peng et al.: Archaeological contexts should not be ignored for early chicken domestication
(2015)