Blimp-1-dependent and -independent natural antibody production by B-1 and B-1-derived plasma cells.

Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1-derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1+, and (c) Blimp-1neg phenotypic B-1 cells. Blimp-1neg IgM-secreting B-1 cells are not simply intermediates of cellular differentiation. Instead, they secrete similar amounts of IgM in wild-type and Blimp-1-deficient (PRDM-1ΔEx1A) mice. Blimp-1neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1 changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus, the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a distinct subset of cells that do not use Blimp-1 for initiation or maximal antibody secretion

The Allometry of Host-Pathogen Interactions

Understanding the mechanisms that control rates of disease progression in humans and other species is an important area of research relevant to epidemiology and to translating studies in small laboratory animals to humans. Body size and metabolic rate influence a great number of biological rates and times. We hypothesize that body size and metabolic rate affect rates of pathogenesis, specifically the times between infection and first symptoms or death.We conducted a literature search to find estimates of the time from infection to first symptoms (t(S)) and to death (t(D)) for five pathogens infecting a variety of bird and mammal hosts. A broad sampling of diseases (1 bacterial, 1 prion, 3 viruses) indicates that pathogenesis is controlled by the scaling of host metabolism. We find that the time for symptoms to appear is a constant fraction of time to death in all but one disease. Our findings also predict that many population-level attributes of disease dynamics are likely to be expressed as dimensionless quantities that are independent of host body size.Our results show that much variability in host pathogenesis can be described by simple power functions consistent with the scaling of host metabolic rate. Assessing how disease progression is controlled by geometric relationships will be important for future research. To our knowledge this is the first study to report the allometric scaling of host/pathogen interactions

The terrestrial evolution of metabolism and life – by the numbers

<p>Abstract</p> <p>Background</p> <p>Allometric scaling relating body mass to metabolic rate by an exponent of the former (<it>Kleiber's Law</it>), commonly known as quarter-power scaling (QPS), is controversial for claims made on its behalf, especially that of its universality for all life. As originally formulated, Kleiber was based upon the study of heat; metabolic rate is quantified in watts (or calories per unit time). Techniques and technology for metabolic energy measurement have been refined but the math has not. QPS is susceptible to increasing deviations from theoretical predictions to data, suggesting that there is no single, universal exponent relevant to all of life. QPS's major proponents continue to fail to make good on hints of the power of the equation for understanding aging.</p> <p>Essentialist-deductivist view</p> <p>If the equation includes a term for efficiency in the exponent, thereby ruling out thermogenesis as part of metabolism, its heuristic power is greatly amplified, and testable deductive inferences are generated. If metabolic rate is measured in watts and metabolic efficiency is a redox-coupling ratio, then the equation is essentially about the energy storage capacity of organic molecules. The equation is entirely about the essentials of all life: water, salt, organic molecules, and energy. The water and salt provide an electrochemical salt bridge for the transmission of energy into and through the organic components. The equation, when graphed, treats the organic structure as battery-like, and relates its recharge rate and electrical properties to its longevity.</p> <p>Conclusion</p> <p>The equation models the longevity-extending effects of caloric restriction, and shows where those effects wane. It models the immortality of some types of cells, and supports the argument for the origin of life being at submarine volcanic vents and black smokers. It clarifies how early life had to change to survive drifting to the surface, and what drove mutations in its ascent. It does not deal with cause and effect; it deals with variables in the essentials of all life, and treats life as an epiphenomenon of those variables. The equation describes how battery discharge into the body can increase muscle mass, promote fitness, and extend life span, among other issues.</p

Sizing Up Allometric Scaling Theory

Metabolic rate, heart rate, lifespan, and many other physiological properties vary with body mass in systematic and interrelated ways. Present empirical data suggest that these scaling relationships take the form of power laws with exponents that are simple multiples of one quarter. A compelling explanation of this observation was put forward a decade ago by West, Brown, and Enquist (WBE). Their framework elucidates the link between metabolic rate and body mass by focusing on the dynamics and structure of resource distribution networks—the cardiovascular system in the case of mammals. Within this framework the WBE model is based on eight assumptions from which it derives the well-known observed scaling exponent of 3/4. In this paper we clarify that this result only holds in the limit of infinite network size (body mass) and that the actual exponent predicted by the model depends on the sizes of the organisms being studied. Failure to clarify and to explore the nature of this approximation has led to debates about the WBE model that were at cross purposes. We compute analytical expressions for the finite-size corrections to the 3/4 exponent, resulting in a spectrum of scaling exponents as a function of absolute network size. When accounting for these corrections over a size range spanning the eight orders of magnitude observed in mammals, the WBE model predicts a scaling exponent of 0.81, seemingly at odds with data. We then proceed to study the sensitivity of the scaling exponent with respect to variations in several assumptions that underlie the WBE model, always in the context of finite-size corrections. Here too, the trends we derive from the model seem at odds with trends detectable in empirical data. Our work illustrates the utility of the WBE framework in reasoning about allometric scaling, while at the same time suggesting that the current canonical model may need amendments to bring its predictions fully in line with available datasets

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns

Charged-Higgs phenomenology in the Aligned two-Higgs-doublet model

The alignment in flavour space of the Yukawa matrices of a general two-Higgs-doublet model results in the absence of tree-level flavour-changing neutral currents. In addition to the usual fermion masses and mixings, the aligned Yukawa structure only contains three complex parameters, which are potential new sources of CP violation. For particular values of these three parameters all known specific implementations of the model based on discrete Z_2 symmetries are recovered. One of the most distinctive features of the two-Higgs-doublet model is the presence of a charged scalar. In this work, we discuss its main phenomenological consequences in flavour-changing processes at low energies and derive the corresponding constraints on the parameters of the aligned two-Higgs-doublet model.Comment: 46 pages, 19 figures. Version accepted for publication in JHEP. References added. Discussion slightly extended. Conclusions unchange

The distribution of pond snail communities across a landscape: separating out the influence of spatial position from local habitat quality for ponds in south-east Northumberland, UK

Ponds support a rich biodiversity because the heterogeneity of individual ponds creates, at the landscape scale, a diversity of habitats for wildlife. The distribution of pond animals and plants will be influenced by both the local conditions within a pond and the spatial distribution of ponds across the landscape. Separating out the local from the spatial is difficult because the two are often linked. Pond snails are likely to be affected by both local conditions, e.g. water hardness, and spatial patterns, e.g. distance between ponds, but studies of snail communities struggle distinguishing between the two. In this study, communities of snails were recorded from 52 ponds in a biogeographically coherent landscape in north-east England. The distribution of snail communities was compared to local environments characterised by the macrophyte communities within each pond and to the spatial pattern of ponds throughout the landscape. Mantel tests were used to partial out the local versus the landscape respective influences. Snail communities became more similar in ponds that were closer together and in ponds with similar macrophyte communities as both the local and the landscape scale were important for this group of animals. Data were collected from several types of ponds, including those created on nature reserves specifically for wildlife, old field ponds (at least 150 years old) primarily created for watering livestock and subsidence ponds outside protected areas or amongst coastal dunes. No one pond type supported all the species. Larger, deeper ponds on nature reserves had the highest numbers of species within individual ponds but shallow, temporary sites on farm land supported a distinct temporary water fauna. The conservation of pond snails in this region requires a diversity of pond types rather than one idealised type and ponds scattered throughout the area at a variety of sites, not just concentrated on nature reserves

Theory of Multidimensional Solitons

We review a number of topics germane to higher-dimensional solitons in Bose-Einstein condensates. For dark solitons, we discuss dark band and planar solitons; ring dark solitons and spherical shell solitons; solitary waves in restricted geometries; vortex rings and rarefaction pulses; and multi-component Bose-Einstein condensates. For bright solitons, we discuss instability, stability, and metastability; bright soliton engineering, including pulsed atom lasers; solitons in a thermal bath; soliton-soliton interactions; and bright ring solitons and quantum vortices. A thorough reference list is included.Comment: review paper, to appear as Chapter 5a in "Emergent Nonlinear Phenomena in Bose-Einstein Condensates: Theory and Experiment," edited by P. G. Kevrekidis, D. J. Frantzeskakis, and R. Carretero-Gonzalez (Springer-Verlag

Industrial energy use and the human life history

The demographic rates of most organisms are supported by the consumption of food energy, which is used to produce new biomass and fuel physiological processes. Unlike other species, modern humans use ‘extra-metabolic' energy sources acquired independent of physiology, which also influence demographics. We ask whether the amount of extra-metabolic energy added to the energy budget affects demographic and life history traits in a predictable way. Currently it is not known how human demographics respond to energy use, and we characterize this response using an allometric approach. All of the human life history traits we examine are significant functions of per capita energy use across industrialized populations. We find a continuum of traits from those that respond strongly to the amount of extra-metabolic energy used, to those that respond with shallow slopes. We also show that the differences in plasticity across traits can drive the net reproductive rate to below-replacement levels