A data-driven framework to model the organism–environment system

Organisms modify their development and function in response to the environment. At the same time, the environment is modified by the activities of the organism. Despite the ubiquity of such dynamical interactions in nature, it remains challenging to develop models that accurately represent them, and that can be fitted using data. These features are desirable when modeling phenomena such as phenotypic plasticity, to generate quantitative predictions of how the system will respond to environmental signals of different magnitude or at different times, for example, during ontogeny. Here, we explain a modeling framework that represents the organism and environment as a single coupled dynamical system in terms of inputs and outputs. Inputs are external signals, and outputs are measurements of the system in time. The framework uses time-series data of inputs and outputs to fit a nonlinear black-box model that allows to predict how the system will respond to novel input signals. The framework has three key properties: it captures the dynamical nature of the organism–environment system, it can be fitted with data, and it can be applied without detailed knowledge of the system. We study phenotypic plasticity using in silico experiments and demonstrate that the framework predicts the response to novel environmental signals. The framework allows us to model plasticity as a dynamical property that changes in time during ontogeny, reflecting the well-known fact that organisms are more or less plastic at different developmental stages.     

The agony of choice: Impact of the host animal species on the enzyme-linked immunosorbent assay performance for host cell protein quantification

Host cell proteins (HCPs) are inevitable process-related impurities in biotherapeutics commonly monitored by enzyme-linked immunosorbent assays (ELISAs). Of particular importance for their reliable detection are the anti-HCP polyclonal antibodies (pAbs), supposed to detect a broad range of HCPs. The present study focuses on the identification of suitable host animal species for the development of high-performance CHO-HCP ELISAs, assuming the generation of pAbs with adequate coverage and specificity. Hence, antibodies derived from immunization of sheep, goats, donkeys, rabbits, and chickens were compared concerning their amount of HCP-specific antibodies, coverage, and performance in a sandwich ELISA. Immunization of sheep, goats, donkeys, and rabbits met all test criteria, whereas the antibodies from chickens cannot be recommended based on the results of this study. Additionally, a mixture of antibodies from the five host species was prepared to assess if coverage and ELISA performance can be improved by a multispecies approach. Comparable results were obtained for the single- and multispecies ELISAs in different in-process samples, indicating no substantial improvement for the latter in ELISA performance while raising ethical and financial concerns.     

A Mycobacterium leprae-specific gene encoding an immunologically recognized 45 kDa protein

By screening a Mycobacterium leprae lambda gt11 expression library with a serum from an Ethiopian lepromatous leprosy (LL) patient a clone was isolated (LL4) belonging to hybridization group III of a panel of previously isolated M. leprae clones. Members of this hybridization group encode a serologically recognized 45 kDa protein. The complete DNA sequences of the partially overlapping clones LL4 and L1 (hybridization group III) are presented and these revealed the presence of an open reading frame (ORF) predicting a protein with a molecular size of 42 448 Da. Southern hybridizations on total genomic DNA of M. Ieprae, Mycobacterium tuberculosis and eight atypical mycobacteria showed that the LL4 DNA fragment is specific for M. Ieprae DNA even under low-stringency conditions. The M. Ieprae specificity of LL4 DNA was further confirmed by the polymerase chain reaction using four different sets of primers. Western blotting analyses showed that the M. Ieprae 45 kDa protein is frequently recognized by antibodies from leprosy patients and that this recognition is specific since no antibodies could be detected in sera of tuberculosis patients. T-cell proliferation assays also demonstrated T-cell recognition by leprosy patients and healthy contacts of the M. Ieprae 45 kDa protein. The specificity of the LL4 DNA region and the 45 kDa antigen that is encoded by hybridization group III could provide unique tools for the development of M. Ieprae-specific immunological and DNA reagents.     

Poleward increase in feeding efficiency of leafminer Stigmella lapponica (Lepidoptera: Nepticulidae) in a latitudinal gradient crossing a boreal forest zone

Damage to plant communities imposed by insect herbivores generally decreases from low to high latitudes. This decrease is routinely attributed to declines in herbivore abundance and/or diversity, whereas latitudinal changes in per capita food consumption remain virtually unknown. Here, we tested the hypothesis that the lifetime food consumption by a herbivore individual decreases from low to high latitudes due to a temperature-driven decrease in metabolic expenses. From 2016 to 2019, we explored latitudinal changes in multiple characteristics of linear (gallery) mines made by larvae of the pygmy moth, Stigmella lapponica, in leaves of downy birch, Betula pubescens. The mined leaves were larger than intact leaves at the southern end of our latitudinal gradient (at 60°N) but smaller than intact leaves at its northern end (at 69°N), suggesting that female oviposition preference changes with latitude. No latitudinal changes were observed in larval size, mine length or area, and in per capita food consumption, but the larval feeding efficiency (quantified as the ratio between larval size and mine size) increased with latitude. Consequently, S. lapponica larvae consumed less foliar biomass at higher latitudes than at lower latitudes to reach the same size. Based on space-for-time substitution, we suggest that climate warming will increase metabolic expenses of insect herbivores with uncertain consequences for plant–herbivore interactions.     

Sodium in gramicidin: an example of a permion.

The reaction path and free energy profile of Na+ were computed in the interior of the channel protein gramicidin, with the program MOIL. Gramicidin was represented in atomic detail, but surrounding water and lipid molecules were not included. Thus, only short range interactions were investigated. The permeation path of the ion was an irregular spiral, far from a straight line. Permeation cannot be described by motions of a single Na+ ion. The minimal energy path includes significant motion of water and channel atoms as well as motion of the permeating ion. We think of permeation as motion of a permion, a quasi-particle that includes the many body character of the permeation process, comparable with quasi-particles like holes, phonons, and electrons of solid-state physics. Na+ is accompanied by a plug of water molecules, and motions of water, Na+, and the atoms of gramicidin are highly correlated. The permion moves like a linear polymer made of waters and ion linked and moving coherently along a zigzag line, following the reptation mechanism of polymer transport. The effective mass, free energy, and memory kernel (of the integral describing time-dependent friction) of short range interactions were calculated. The effective mass of the permion (properly normalized) is much less than Na+. Friction varies substantially along the path. The free energy profile has two deep minima and several maxima. In certain regions, the dominant motions along the reaction path are those of the channel protein, not the permeating ion: there, ion waits while the other atoms move. At these waiting sites, the permion's motion along the reaction path is a displacement of the atoms of gramicidin that prepare the way for the Na+ ion.     

Fossil Homo femur from Berg Aukas,northern Namibia

The proximal half of a hominid femur was recovered from deep within a paleokarst feature at the Berg Aukas mine, northern Namibia. The femur is fully mineralized, but it is not possible to place it in geochrono logical context. It has a very large head, an exceptionally thick diaphyseal cortex, and a very low collodiaphyseal angle, which serve to differentiate it from Holocene homologues. The femur is not attributable to Australopithecus, Paranthropus, or early Homo (i.e., H. habilis sensu lato). Homo erectus femora have a relatively longer and AP flatter neck, and a shaft that exhibits less pilaster than the Berg Aukas specimen. Berg Aukas also differs from early modern femora in several features, including diaphyseal cortical thickness and the degree of subtrochanteric AP flattening. The massive diaphyseal cortex of Berg Aukas finds its closest similarity within archaic H. sapiens (e.g., Castel di Guido) and H. erectus (e.g., KNM-ER 736) samples. It has more cortical bone at midshaft than any other specimen, although relative cortical thickness and the asymmetry of its cross-sectional disposition at this level are comparable with those of other Pleistocene fem ora. The closest morphological comparisons with Berg Aukas are in archaic (i.e., Middle Pleistocene) H. sapiens and Neandertal samples. © 1995 Wiley-Liss, Inc.     

Regulation of the host response to bacterial lipopolysaccharides

Bacterial endotoxins or lipopolysaccharides (LPS) are unique glycolipids present in the outer cell membrane of all gram-negative bacteria. It is now generally recognized that LPS is of primary importance in initiating the pathophysiological changes that often accompany gram-negative bacillary infections in humans including hypotensive shock, disseminated intravascular coagulation, and metabolic abnormalities. Although the biochemical mechanisms of these changes are not well understood, increasing emphasis has been placed on defining the biochemical response of the macrophage (M phi) to LPS. In this paper we describe two M phi-derived factors induced by LPS that may be important in the expression of endotoxic activity in the host. These are a procoagulant activity, which is present on the cell membrane of LPS-treated rabbit liver M phi and acts by directly activating coagulation factor X, and a factor released into the supernatant by LPS-treated peritoneal exudate M phi, which suppresses steroidogenesis in explanted adrenocortical cells. The potential role of the M phi in regulating the binding of LPS to high-density lipoproteins through the induction of acute phase proteins is also considered.