Catch-bond mechanism of force-enhanced adhesion: counterintuitive, elusive, but ... widespread?

Catch bonds are bonds between a ligand and its receptor that are enhanced by mechanical force pulling the ligand-receptor complex apart. To date, catch-bond formation has been documented for the most common Escherichia coli adhesin, FimH, and for P-/L-selectins, universally expressed by leukocytes, platelets, and blood vessel walls. One compelling explanation for catch bonds is that force-induced structural alterations in the receptor protein are allosterically linked to a high-affinity conformation of its ligand-binding pocket. Catch-bond properties are likely to be widespread among adhesive proteins, thus calling for a detailed understanding of their underlying mechanisms and physiological significance.     

ArchbotLit—the archaeobotanical literature database: an update of the search engine for literature on archaeological remains of cultivated plants since 1981

Vegetation History and Archaeobotany - The online Archaeobotanical Literature Database (ArchbotLit) is an important tool for getting targeted access to archaeobotanical publications. It offers the...     

A search for protein cores in chromosomes: Is the scaffold an artifact?

A protein chromosome scaffold structure has been proposed that acts as a structural framework for attachment of chromosomal DNA. There are several troubling aspects of this concept: (1) such structures have not been seen in many previous thin-section and whole-mount electron microscopy studies of metaphase chromosomes, while they are readily seen in leptotene and zygotene chromosomes; (2) such a structure poses problems for sister chromatid exchanges; and (3) the published photographs show a marked variation in the amount of scaffold in different whole-mount preparations. An alternative explanation is that the scaffold in whole-mount preparations represents incomplete dispersion of the high concentration of chromatin in the center of chromosomes, and when the histones are removed and the DNA dispersed, the remaining nonhistone proteins (NHPs) aggregate to form a chromosome-shaped structure. Two studies were done to determine if the scaffold is real or an artifact: (1) Chinese hamster mitotic cells and isolated chromosomes were examined using two protein stains -EDTA-regressive staining and phosphotungstic acid (PTA) stain. The EDTA-regressive stain showed ribonucleoprotein particles at the periphery of the chromosomes but nothing at the center of the chromosomes. The PTA stain showed the kinetochore plates but no central structures; and (2) isolated chromosomes were partially dispersed to decrease the high concentration of chromatin in the center of the chromosome, then treated with 4 M ammonium acetate or 2 M NaCl to dehistonize them and disperse the DNA. Under these circumstances, no chromosome scaffold was seen. We conclude that the scaffold structure is an artifact resulting from incomplete dispersion of central chromatin and aggregation of NHPs in dehistonized chromosomes.     

An elusive paleodemography? A comparison of two methods for estimating the adult age distribution of deaths at late Classic Copan,Honduras

Comparison of different adult age estimation methods on the same skeletal sample with unknown ages could forward paleodemographic inference, while researchers sort out various controversies. The original aging method for the auricular surface (Lovejoy et al., 1985a) assigned an age estimation based on several separate characteristics. Researchers have found this original method hard to apply. It is usually forgotten that before assigning an age, there was a seriation, an ordering of all available individuals from youngest to oldest. Thus, age estimation reflected the place of an individual within its sample. A recent article (Buckberry and Chamberlain, 2002) proposed a revised method that scores theses various characteristics into age stages, which can then be used with a Bayesian method to estimate an adult age distribution for the sample. Both methods were applied to the adult auricular surfaces of a Pre-Columbian Maya skeletal population from Copan, Honduras and resulted in age distributions with significant numbers of older adults. However, contrary to the usual paleodemographic distribution, one Bayesian estimation based on uniform prior probabilities yielded a population with 57% of the ages at death over 65, while another based on a high mortality life table still had 12% of the individuals aged over 75 years. The seriation method yielded an age distribution more similar to that known from preindustrial historical situations, without excessive longevity of adults. Paleodemography must still wrestle with its elusive goal of accurate adult age estimation from skeletons, a necessary base for demographic study of past populations.     

Insights into plant consciousness from neuroscience,physics and mathematics: A role for quasicrystals?

There is considerable debate over whether plants are conscious and this, indeed, is an important question. Here I look at developments in neuroscience, physics and mathematics that may impact on this question. Two major concomitants of consciousness in animals are microtubule function and electrical gamma wave synchrony. Both these factors may also play a role in plant consciousness. I show that plants possess aperiodic quasicrystal structures composed of ribosomes that may enable quantum computing, which has been suggested to lie at the core of animal consciousness. Finally I look at whether a microtubule fractal suggests that electric current plays a part in conventional neurocomputing processes in plants.     

Does consciousness really collapse the wave function?: A possible objective biophysical resolution of the measurement problem

An analysis has been performed of the theories and postulates advanced by von Neumann, London and Bauer, and Wigner, concerning the role that consciousness might play in the collapse of the wave function, which has become known as the measurement problem. This reveals that an error may have been made by them in the area of biology and its interface with quantum mechanics when they called for the reduction of any superposition states in the brain through the mind or consciousness. Many years later Wigner changed his mind to reflect a simpler and more realistic objective position which appears to offer a way to resolve this issue. The argument is therefore made that the wave function of any superposed photon state or states is always objectively and stochastically changed within the complex architecture of the eye in a continuous linear process initially for most of the superposed photons, followed by a discontinuous nonlinear collapse process later for any remaining superposed photons, thereby guaranteeing that only final, measured information is presented to the brain, mind or consciousness. An experiment to be conducted in the near future may enable us to simultaneously resolve the measurement problem and also determine if the linear nature of quantum mechanics is violated by the perceptual process.     

A century of research into the cause of cancer: is the new oncogene paradigm revolutionary?

Contemporary oncological research is predominantly characterised by genetic explanations, a situation which may be briefly denoted as the oncogene paradigm. This essay discusses why the new paradigm was perceived so attractive that it could take over the whole field of oncology within a time-span of less than two decades. It is argued that the revolutionary character of the oncogene paradigm stems from the fact that it transcends a dichotomy which has kept experimental cancer research divided for more than three quarters of a century. This concerns the dichotomy between so-called exogenous and endogenous explanations of cancer causation. This essay mainly focuses on the role of the exogenous/endogenous dichotomy in the reception of research on oncogenic viruses, especially discussing the work of Nobel laureate Peyton Rous on cancer viruses at the Rockefeller Institute. Rous was severely criticised by James Ewing, director of the Memorial Hospital for Cancer and Allied Diseases in New York, who held the idea that the origin of cancer was based in the cell. The twentieth century controversy over oncogenic viruses is placed in the context of the intense discussion over causality in medicine during the first decades of the twentieth century in Germany. It is argued that the oncogene paradigm may be seen as revolutionary because it succeeded in uniting the exogenous and endogenous explanations of cancer in a single paradigm.     

Towards an ecological understanding of the killer trait – A reproducible protocol for testing its impact on freshwater ciliates

Paramecium strains with the ability to kill other paramecia often harbour intracellular bacteria belonging to the genera Caedibacter or Caedimonas. Central structures of this killer trait are refractile bodies (R-bodies) produced by the endosymbionts. Once ingested by a sensitive Paramecium, R-bodies presumably act as delivery system for an unidentified toxin which causes the death of endosymbiont-free paramecia while those infected gain resistance from their symbionts. The killer trait is therefore considered as competitive advantage for the hosts of R-body producers. While its effectiveness against paramecia is well documented, the effects on other aquatic ciliates are much less studied.In order to address the broadness of the killer trait, a reproducible killer test assay considering the effects on predatory ciliates (Climacostomum virens and Dileptus jonesi) as well as potential bacterivorous Paramecium competitors (Dexiostoma campyla, Euplotes aediculatus, Euplotes woodruffi, and Spirostomum teres) as possibly susceptible species was established. All used organisms were molecularly characterized to increase traceability and reproducibility. The absence of any lethal effects in both predators and competitors after exposure to killer paramecia strongly suggests a narrow action range for the killer trait. Thus, R-body producing bacteria provide their host with a complex, costly strategy to outcompete symbiont-free congeners only.     

Mechanisms of hepatic transport of cyclosporin A: an explanation for its cholestatic action?

The hepatic transport of the immunosuppressive Cyclosporin A (CyA) was studied using liposomal phospholipid membranes, freshly isolated rat hepatocytes and bile canalicular plasma membrane vesicles from rat liver. The Na(+)-dependent, saturable uptake of the bile acid 3H-taurocholate into isolated rat liver cells was apparently competitively inhibited by CyA. However, the uptake of CyA into the cells was neither saturable, nor temperature-dependent nor Na(+)-dependent, nor could it be inhibited by bile salts or CyA-derivatives, indicating passive diffusion. In steady state depolarization fluorescence studies, CyA caused a concentration-dependent decrease of anisotropy, indicating a membrane fluidizing effect. Ion flux experiments demonstrated that CyA dramatically increases the permeability of Na+ and Ca2+ across phospholipid membranes in a dose- and time-dependent manner, suggesting a iontophoretic activity that might have a direct impact on cellular ion homeostasis and regulation of bile acid uptake. Photoaffinity labeling with a [3H]-labeled photolabile CyA-derivative resulted in the predominant incorporation of radioactivity into a membrane polypeptide with an apparent molecular weight of 160,000 and a minor labeling of polypeptides with molecular weights of 85,000-90,000. In contrast, use of a photolabile bile acid resulted in the labeling of a membrane polypeptide with an apparent molecular weight of 110,000, representing the bile canalicular bile acid carrier. The photoaffinity labeling as well as CyA transport by canalicular membrane vesicles were inhibited by CyA and the p-glycoprotein substrates daunomycin and PSC-833, but not by taurocholate, indicating that CyA is excreted by p-glycoprotein. CyA uptake by bile canalicular membrane vesicles was ATP-dependent and could not be inhibited by taurocholate. CyA caused a decrease in the maximum amount of bile salt accumulated by the vesicles with time. However, initial rates of [3H]-taurocholate uptake within the first 2.5 min remained unchanged at increasing CyA concentrations. In summary, the data indicate that CyA does not directly interact with the hepatic bile acid transport systems. Its cholestatic action may rather be the result of alterations in membrane fluidity, intracellular effects and an interaction with p-glycoprotein.     

Compassion for animals in the laboratory: impairment or refinement of research methodology?

There are now signs in the United States as well as in Europe that the importance of a positive human-nonhuman animal relationship in research laboratories is appreciated more seriously. In addition to knowledge and skills, primary attributes of animal research personnel must be feelings of compassion and sensitivity toward animals to safeguard the reliability of scientific research data.     

Can rabbits tell humans apart?: Discrimination of individual humans and its implications for animal research

To predict when food reward was available, 12 New Zealand White rabbits were trained to discriminate between two humans. All subjects had significantly higher response rates and greater behavioral arousal in the presence of the positive stimulus person. The ability to discriminate between individual humans sets the stage for unanticipated Pavlovian conditioning, which may have considerable implications for animal research in behavioral and biomedical settings.