Evaluating the connectivity, continuity and distance norm in mathematical models for community ecology, epidemiology and multicellular pathway prediction

The main global threats of the biosphere on our planet, such as a global biodiversity impairment, global health issues in the developing countries, associated with an environmental decay, unnoticed in previous eras, the rise of greenhouse gasses and global warming, urge for a new evaluation of the applicability of mathematical modelling in the physical sciences and its benefits for society. In this paper, we embark on a historical review of the mathematical models developed in the previous century, that were devoted to the study of the geographical spread of biological infections. The basic notions of connectivity, continuity and distance norm as applied by successive bio-mathematicians, starting with the names of Volterra, Turing and Kendall, are highlighted in order to demonstrate their usefulness in several new areas of bio-mathematical research. These new areas include the well-known fields of community ecology and epidemiology, but also the less well-known field of multicellular pathway prediction. The biological interpretation of these abstract mathematical notions, as well as the methodological criteria for these interpretative schemes and their corroboration with empirical evidence are discussed. In particular, we will focus on the boundedness norm in polynomial Lyapunov functions and its application in Markovian models for community assembly and in models f

Immunohistochemical, morphological and ultrastructural resemblance between dendritic cells and folliculo-stellate cells in normal human and rat anterior pituitaries

Immunolabeling of cryo-sections of human anterior pituitaries obtained at autopsy, and of cryo-sections of freshly prepared rat anterior pituitaries, with a panel of monoclonal antibodies against markers of the monocyte/dendritic cell/macrophage lineage, reveals in both species a characteristic pattern of immunopositive cells, among which many cells with dendritic phenotype are found. Cells characterized by marker expression of MHC-class II determinants and a dendritic morphology are present in both human and rat anterior pituitary. Markers characteristic of dendritic cells such as the L25 antigen and the OX62 antigen were present in anterior pituitaries from human and rat respectively. The population of MHC-class II expressing dendritic cells of the rat anterior pituitary is compared at the ultrastructural level with the folliculo-stellate cell population, which cell type has been previously characterized by its distinctive ultrastructure and immunopositivity for the S100 protein. Using immune-electron microscopy of rat anterior pituitaries fixed with periodate-lysine-paraformaldehyde, we were able to distinguish non-granulated cells expressing MHC-class II determinants, whereas no MHC-class II expression was found in the granulated endocrine cells. Using double immunolabeling of cryo-sections of these rat AP with 25 nm and 15 nm gold labels, we demonstrated an overlap between the populations of MHC-class II-expressing and S100 protein-expressing cells. Furthermore, MHC-class II-expressing and S100-positive cells showed ultrastructural characteristics that have been previously ascribed to folliculo-stellate cells. At the light microscopical level in the rat AP, a proportion of 10 to 20% of the S100-positive cells was found immunopositive for the MHC-class II marker OX6. In the hu

Lessons learned in coupling atmospheric models across scales for onshore and offshore wind energy

The Mesoscale to Microscale Coupling team, part of the U.S. Department of Energy Atmosphere to Electrons (A2e) initiative, has studied various important challenges related to coupling mesoscale models to microscale models for the use case of wind energy development and operation. Several coupling methods and techniques for generating turbulence at the microscale that is subgrid to the mesoscale have been evaluated for a variety of cases. Case studies included flat-terrain, complex-terrain, and offshore environments. Methods were developed to bridge the terra incognita, which scales from about 100 m through the depth of the boundary layer. The team used wind-relevant metrics and archived code, case information, and assessment tools and is making those widely available. Lessons learned and discerned best practices are described in the context of the cases studied for the purpose of enabling further deployment of wind energy.</p

Skewed Exposure to Environmental Antigens Complements Hygiene Hypothesis in Explaining the Rise of Allergy

The Hygiene Hypothesis has been recognized as an important cornerstone to explain the sudden increase in the prevalence of asthma and allergic diseases in modernized culture. The recent epidemic of allergic diseases is in contrast with the gradual implementation of Homo sapiens sapiens to the present-day forms of civilization. This civilization forms a gradual process with cumulative effects on the human immune system, which co-developed with parasitic and commensal Helminths. The clinical manifestation of this epidemic, however, became only visible in the second half of the twentieth century. In order to explain these clinical effects in terms of the underlying IgE-mediated reactions to innocuous environmental antigens, the low biodiversity of antigens in the domestic environment plays a pivotal role. The skewing of antigen exposure as a cumulative effect of reducing biodiversity in the immediate human environment as well as in changing food habits, provides a sufficient and parsimonious explanation for the rise in allergic diseases in a highly developed and helminth-free modernized culture. Socio-economic tendencies that incline towards a further reduction of environmental biodiversity may provide serious concern for future health. This article explains that the “Hygiene Hypothesis”, the “Old Friends Hypothesis”, and the “Skewed Antigen Exposure Hypothesis” are required to more fully explain the rise of allergy in modern societies

A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary

BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease

Biophysical parameters affecting lung surfactant function, surface tension and the transition from aerosol to droplet exhalation (in relation to COVID-19 infection)

A considerable number of biophysical and biochemical studies has increased our understanding of the surface activity of surfactant proteins B and C (SP-B, SP-C) in the (mammalian) lung and their importance for a healthy, proper breathing system. For instance, it is well-known that these surfactant proteins are released from the lamellar bodies of type II cells of the lung alveoli (type II pneumocytes), and that at compression, the lipid-protein monolayer of the surfactant is squeezed into three-dimensional (3D) stacks, acting as a surfactant reservoir. Moreover, studies have demonstrated the influence of hydrophobic nanoparticles on lung surfactant model systems, well before the outbreak of the COVID-19 pandemic. The potentially devastating effect of SARS-CoV-2 infection on vital lung function, including pneumonia and Acute respiratory distress syndrome (ARDS), meanwhile has been confirmed worldwide by thousands of fatal cases, although the mechanism of its onset is not completely understood. In theory, any virus carrying palmitoylated spike proteins (like beta-coronaviruses in general) might interfere with the alveolar surface activity, when infecting the deep respiratory system. However, it is clearly established that SARS-CoV-2 uses the Angiotensin converting enzyme 2 receptor (ACE2) for entry in the host, which receptor is expressed on the same type II pneumocytes, and, as a result, the virus may directly interfere with the secretion of surfactant proteins. This study aims at elucidating the main targets for containment of the spread of the SARS-CoV-2 virus via the respiratory system, a better understanding of the role of virus-surfactant interactions, the formation of aerosols and role of the inflammatory components of the immune system, as well as the role of positive pressure ventilation systems on particle exhalation, as being used at ICUs. Finally, suggestions are made for important goals for future biophysics research in infectious disease prevention and containment

Trichilemmal keratinisation: a causal factor in loosening the murine telogen club hair from the trichilemmal sac.

A quantitative histochemical study was carried out on the distribution of protein thiol and disulphide groups in the telogen follicle of mice. The histochemical demonstration of reactive groups was achieved by a method first described by Sippel (1973). The histological observations support former views on trichilemmal keratinisation that trichilemmal cells are the main site of thiol groups and that the hair club itself appears to be the most prominent site of disulphide cross linkages. The histophotometric data reveal an increase in thiol-disulphide conversion which coincides with the development of a succeeding hair generation in the trichilemmal sac of the telogen follicle. On the basis of this observation, it is suggested that trichilemmal keratinisation is a causal factor in loosening the old club hair from its trichilemmal sac, a process which is probably similar to the sloughing of cornified epidermal cells