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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)
When local poverty is more important than your income: Mental health in minorities in inner cities
(2015)
Charges dropped
(2015)
The quintuplet cluster III. Hertzsprung-Russell diagram and cluster age (vol 540, pg A14, 2012)
(2014)
We study the parameter sensitivity of hetero-polymeric DNA within the purview of DNA breathing dynamics. The degree of correlation between the mean bubble size and the model parameters is estimated for this purpose for three different DNA sequences. The analysis leads us to a better understanding of the sequence dependent nature of the breathing dynamics of hetero-polymeric DNA. Out of the 14 model parameters for DNA stability in the statistical Poland-Scheraga approach, the hydrogen bond interaction epsilon(hb)(AT) for an AT base pair and the ring factor. turn out to be the most sensitive parameters. In addition, the stacking interaction epsilon(st)(TA-TA) for an TA-TA nearest neighbor pair of base-pairs is found to be the most sensitive one among all stacking interactions. Moreover, we also establish that the nature of stacking interaction has a deciding effect on the DNA breathing dynamics, not the number of times a particular stacking interaction appears in a sequence. We show that the sensitivity analysis can be used as an effective measure to guide a stochastic optimization technique to find the kinetic rate constants related to the dynamics as opposed to the case where the rate constants are measured using the conventional unbiased way of optimization.
HESS J1640-465 - an exceptionally luminous TeV gamma-ray supernova remnant (vol 439, pg 2828, 2014)
(2014)
P>Despite ample research, understanding plant spread and predicting their ability to track projected climate changes remain a formidable challenge to be confronted. We modelled the spread of North American wind-dispersed trees in current and future (c. 2060) conditions, accounting for variation in 10 key dispersal, demographic and environmental factors affecting population spread. Predicted spread rates vary substantially among 12 study species, primarily due to inter-specific variation in maturation age, fecundity and seed terminal velocity. Future spread is predicted to be faster if atmospheric CO2 enrichment would increase fecundity and advance maturation, irrespective of the projected changes in mean surface windspeed. Yet, for only a few species, predicted wind-driven spread will match future climate changes, conditioned on seed abscission occurring only in strong winds and environmental conditions favouring high survival of the farthest-dispersed seeds. Because such conditions are unlikely, North American wind-dispersed trees are expected to lag behind the projected climate range shift.
Data limitations can lead to unrealistic fits of predictive species distribution models (SDMs) and spurious extrapolation to novel environments. Here, we want to draw attention to novel combinations of environmental predictors that are within the sampled range of individual predictors but are nevertheless outside the sample space. These tend to be overlooked when visualizing model behaviour. They may be a cause of differing model transferability and environmental change predictions between methods, a problem described in some studies but generally not well understood. We here use a simple simulated data example to illustrate the problem and provide new and complementary visualization techniques to explore model behaviour and predictions to novel environments. We then apply these in a more complex real-world example. Our results underscore the necessity of scrutinizing model fits, ecological theory and environmental novelty.
Various techniques are utilized by the seismological community, extractive industries, energy and geoengineering companies to identify earthquake nucleation processes in close proximity to engineering operation points. These operations may comprise fluid extraction or injections, artificial water reservoir impoundments, open pit and deep mining, deep geothermal power generations or carbon sequestration. In this letter to the editor, we outline several lines of investigation that we suggest to follow to address the discrimination problem between natural seismicity and seismic events induced or triggered by geoengineering activities. These suggestions have been developed by a group of experts during several meetings and workshops, and we feel that their publication as a summary report is helpful for the geoscientific community. Specific investigation procedures and discrimination approaches, on which our recommendations are based, are also published in this Special Issue (SI) of Journal of Seismology.
Philippine hornbills of the genera Aceros and Penelopides (Bucerotidae) are known to possess a large tandemly duplicated fragment in their mitochondrial genome, whose paralogous parts largely evolve in concert. In the present study, we surveyed the two distinguishable duplicated control regions in several individuals of the Luzon Tarictic Hornbill Penelopides manillae, compare their characteristics within and across individuals, and report on an intraspecific mitochondrial gene rearrangement found in one single specimen, i.e., an interchange between the two control regions. To our knowledge, this is the first observation of two distinct mitochondrial genome rearrangements within a bird species. We briefly discuss a possible evolutionary mechanism responsible for this pattern, and highlight potential implications for the application of control region sequences as a marker in population genetics and phylogeography.