Anticooperativity in diffusion-controlled reactions with pairs of anisotropic domains: a model for the antigen-antibody encounter

The encounter between anisotropic agents in diffusion-controlled reactions is a topic of very general relevance in chemistry and biology. Here we introduce a simplified model of encounter of an isotropic molecule with a pair of partially reacting agents and apply it to the encounter reaction between an antibody and its antigen. We reduce the problem to the solution of dual series relations, which can be solved iteratively, yielding the exact solution for the encounter rate constant at any desired order of accuracy. We quantify the encounter effectiveness by means of a simple indicator and show that the two binding centers systematically behave in an anticooperative fashion. However, we demonstrate that a reduction of the binding active sites allows the composite molecule to recover binding effectiveness, in spite of the overall reduction of the rate constant. In addition, we provide a simple formula that enables one to calculate the anticooperativity as a function of the size of the binding site for any values of the separation between the two active lobes and of the antigen size. Finally, some biological implications of our results are discusse

A nonparametric Bayesian approach toward robot learning by demonstration

In the past years, many authors have considered application of machine learning methodologies to effect robot learning by demonstration. Gaussian mixture regression (GMR) is one of the most successful methodologies used for this purpose. A major limitation of GMR models concerns automatic selection of the proper number of model states, i.e., the number of model component densities. Existing methods, including likelihood- or entropy-based criteria, usually tend to yield noisy model size estimates while imposing heavy computational requirements. Recently, Dirichlet process (infinite) mixture models have emerged in the cornerstone of nonparametric Bayesian statistics as promising candidates for clustering applications where the number of clusters is unknown a priori. Under this motivation, to resolve the aforementioned issues of GMR-based methods for robot learning by demonstration, in this paper we introduce a nonparametric Bayesian formulation for the GMR model, the Dirichlet process GMR model. We derive an efficient variational Bayesian inference algorithm for the proposed model, and we experimentally investigate its efficacy as a robot learning by demonstration methodology, considering a number of demanding robot learning by demonstration scenarios

Massive migration from the steppe is a source for Indo-European languages in Europe

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe

Iron Age and Anglo-Saxon genomes from East England reveal British migration history

British population history has been shaped by a series of immigrations, including the early Anglo-Saxon migrations after 400 CE. It remains an open question how these events affected the genetic composition of the current British population. Here, we present whole-genome sequences from 10 individuals excavated close to Cambridge in the East of England, ranging from the late Iron Age to the middle Anglo-Saxon period. By analysing shared rare variants with hundreds of modern samples from Britain and Europe, we estimate that on average the contemporary East English population derives 38% of its ancestry from Anglo-Saxon migrations. We gain further insight with a new method, rarecoal, which infers population history and identifies fine-scale genetic ancestry from rare variants. Using rarecoal we find that the Anglo-Saxon samples are closely related to modern Dutch and Danish populations, while the Iron Age samples share ancestors with multiple Northern European populations including Britain

Microbial differences between dental plaque and historic dental calculus are related to oral biofilm maturation stage

Dental calculus, calcified oral plaque biofilm, contains microbial and host biomolecules that can be used to study historic microbiome communities and host responses. Dental calculus does not typically accumulate as much today as historically, and clinical oral microbiome research studies focus primarily on living dental plaque biofilm. However, plaque and calculus reflect different conditions of the oral biofilm, and the differences in microbial characteristics between the sample types have not yet been systematically explored. Here, we compare the microbial profiles of modern dental plaque, modern dental calculus, and historic dental calculus to establish expected differences between these substrates.- Background - Results -- Authentication of a preserved oral biofilm in calculus samples -- Dental calculus and plaque biofilm communities are distinct -- Health-associated communities of dental plaque and calculus are distinct -- Signatures of health and of disease are shared in modern and historic calculus samples -- Microbial community differences between health and disease in calculus are poorly resolved -- Absence of caries-specific microbial profiles in dental calculus -- Microbial co-exclusion patterns in plaque and calculus reflect biofilm maturity -- Microbial complexes in plaque and calculus -- Functional prediction in calculus is poorly predictive of health status -- Proteomic profiles of historic healthy site calculus -- Correlations between taxonomic, proteomic, and metabolomic profiles - Discussion - Conclusions - Materials and methods --Historic and modern calculus sample collection DNA extraction -- DNA library construction and high-throughput sequencing -- DNA sequence processing -- Genetic assessment of historic calculus sample preservation -- Genetic microbial taxonomic profiling -- Principal component analysis -- Assessment of differentially abundant taxa -- Sparse partial least squares-discriminant analysis -- Assessment of microbial co-exclusion patterns -- Gene functional categorization with SEED -- Proteomics -- Metabolomics -- Regularized canonical correlation analysi

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Navigating inland: Bronze Age watercraft and the lakes of southern Sweden

The rock art of southern Scandinavia is characterized by depictions of watercraft. The majority are close to the coast, and they have been the primary focus of research. Less attention has been paid to similar representations associated with two large inland lakes in southern Sweden. In this article we present the results of fieldwork around Lake Vänern and Lake Vättern and consider the relationship of this rock art to the better-known images on the coast. We explore the practicalities of navigating between the sea and the interior and suggest that there was an important contrast between an early eastern sphere extending to Lake Vättern from the Baltic and a later western sphere connecting Lake Vänern with the Atlantic.Les représentations d'embarcations caractérisent l'art rupestre de la Scandinavie méridionale. La plupart se trouvent en zone côtière et les recherches ont principalement porté sur celles-ci. On a accordé moins d'attention à des images semblables associées à deux grands lacs intérieurs du sud de la Suède. Dans cet article, les auteurs présentent les résultats d'enquêtes menées autour des lacs Vänern et Vättern et considèrent les liens qui auraient pu exister entre les représentations de cette région et celles, mieux connues, des côtes suédoises. Ils examinent les aspects pratiques d'une navigation entre les côtes et l'intérieur du pays et proposent qu'un contraste significatif existait entre une sphère orientale précoce allant de la Baltique au Lac Vättern et une sphère occidentale plus tardive reliant l'Atlantique au Lac Vänern. Translation by Madeleine HummlerBilder von Wasserfahrzeugen prägen die Felskunst Südskandinaviens. Meistens befinden sich diese Darstellungen in der Nähe der Küsten und deswegen haben diese den Schwerpunkt der Forschung gebildet. Es gibt weniger Forschungsarbeiten über ähnliche Bilder, die mit zwei großen Binnenseen in Südschweden verbunden sind. In diesem Artikel werden die Ergebnisse von Feldarbeiten rund um den Vänern und Vättern vorgestellt und den Zusammenhang zwischen den Darstellungen der Gegend und den besser bekannten Bildern der Küsten betrachtet. Die praktischen Aspekte der Schifffahrt zwischen den Küsten und dem Binnenland werden erwogen und den Standpunkt, dass es einen deutlichen Unterschied zwischen einem frühen östlichen Kreis von der Ostsee bis zum Vättern und einem späteren westlichen Kreis vom Vänern bis zur atlantischen Küste gab, wird vertreten. Translation by Madeleine Hummler</p

Assessment of iron bioavailability from different bread making processes using an in vitro intestinal cell model

Myo-inositol hexakisphosphate (IP6), is the main iron chelator in cereals and bread. The aim of this study was to investigate the effect of three commercial baking processes (sourdough, conventional yeast and Chorleywood Bread Making Process (CBP)) on the IP6 content of wholemeal bread, its impact on iron uptake in Caco-2 cells and the predicted bioavailability of iron from these breads with added iron, simulating a mixed-meal. The sourdough process fully degraded IP6 whilst the CBP and conventional processes reduced it by 75% compared with wholemeal flour. The iron released in solution after a simulated digestion was 8-fold higher in sourdough bread than with others but no difference in cellular iron uptake was observed. Additionally, when iron was added to the different breads digestions only sourdough bread elicited a significant ferritin response in Caco-2 cells (4.8-fold compared to the other breads) suggesting that sourdough bread could contribute towards improved iron nutrition