An enduring association? Microfilariae and immunosuppression [correction of immunosupression] in lymphatic filariasis

Human filarial infection is characterized by a defect in T-cell proliferative responses which is most pronounced among actively infected individuals. This article reviews the immunomodulatory potential of the first larval stage, the blood-borne microfilariae, which has long been associated with the most profound suppression of cellular responses. In particular, we focus on the induction of host cell apoptosis following murine infection with microfilariae. Promoting the apoptotic elimination of potentially reactive T cells could represent an important means of both facilitating parasite survival and limiting inflammatory pathology.     

Diversity in Defining End of Life Care: An Obstacle or the Way Forward?

Aim

The terms used to describe care at the end of life (EoL), and its definitions, have evolved over time and reflect the changes in meaning the concept has undergone as the field develops. We explore the remit of EoL care as defined by experts in EoL care, from across Europe and beyond, to understand its current usage and meanings.

Method

A qualitative survey attached to a call for expertise on cultural issues in EoL care was sent to experts in the field identified through the literature, European EoL care associations, and conferences targeted at EoL care professionals. Respondents were asked to identify further contacts for snowball recruitment.The responses were analysed using content and discourse analysis.

Results

Responses were received from 167 individuals (33% response rate), mainly from academics (39%) and clinical practitioners working in an academic context (23%) from 19 countries in Europe and beyond. 29% of respondents said explicitly that there was no agreed definition of EoL care in practice and only 14% offered a standard definition (WHO, or local institution). 2% said that the concept of EoL care was not used in their country, and 5% said that there was opposition to the concept for religious or cultural reasons. Two approaches were identified to arrive at an understanding of EoL care: exclusively by drawing boundaries through setting time frames, and inclusively by approaching its scope in an integrative way. This led to reflections about terminology and whether defining EoL care is desirable.

Conclusion

The global expansion of EoL care contributes to the variety of interpretations of what it means. This complicates the endeavour of defining the field. However, when diversity is taken seriously it can open up new perspectives to underpin the ethical framework of EoL care.     

An error catastrophe in cancer?

A comparison between the evolution of cancer cell populations and RNA viruses reveals a number of remarkable similarities. Both display high levels of plasticity and adaptability as a consequence of high degrees of genetic variation. It has been suggested that, as it occurs with RNA viruses, there is a threshold in the levels of genetic instability affordable by cancer cells in order to be able to overcome selection barriers (Trends Genet. 15 (1999) M57). Here we explore this concept by means of a simple mathematical model. It is shown that an error threshold exists in this model, which investigates both competition between cancer cell populations and its impact on overall tumor growth dynamics. Once the threshold is reached, the highly unstable tumor cell populations, which were sustaining malignant growth, become unable to maintain their genetic information, which in turn triggers a slowed down overall tumor growth regime.     

Does [3H]Nifedipine Label the Calcium Channel in Rabbit Myocardium?

Abstract

The ionic and drug specificities of the [³H]nifedipine binding site in rabbit cardiac homogenates were investigated. Divalent cations inhibited specific [³H]nifedipine binding in the potency order: Ni⁺² > Ca⁺² ≥ Mg⁺². Monovalent cations did not affect binding. The inorganic calcium entry blocker La⁺³ (IC₅₀ = 1.1 mM) was the most potent cation in inhibiting radioligand binding. Calcium entry blocking drugs of different chemical classes inhibited [³H]-nifedipine binding, with a rank potency order of: nifedipine >> D600 = verapamil > tiapamil > cinnarizine = prenylamine. The same potency order was observed for these drugs in inducing negative inotropic activity of isolated, electrically stimulated rabbit papillary muscle. The stereoselectivity of verapamil and D600 ((?) >> (+) isomers) in depressing papillary muscle contractions was not seen in [³H]nifedipine competition experiments. This presents an obstacle to accepting the equivalence of the [³H]nifedipine binding site with the myocardial Ca⁺² channel. It is, however, possible that the myocardial Ca⁺² channel may be associated with multiple sites of action for calcium entry blockers.     

An Adaptive Immune Response in Drosophila?

The ability to mount an adaptive immune response is thought to be an attribute restricted to vertebrates. A new study conducted in Drosophila demonstrates that invertebrate immunity can adapt to an immune challenge and mount a specific immune response.     

An intracellular actin motor in bacteria?

Actin performs structural as well as motor-like functions in eukaryotic cells. Orthologues of actin have also been identified in bacteria, where they perform an essential function during cell growth. Bacterial actins are implicated in the maintenance of rod-shaped cell morphology, and appear to form a cytoskeletal structure, localising as helical filaments underneath the cell membrane. Recently, a plasmid-borne actin orthologue has been shown to perform a mitotic-like function during segregation of a plasmid, and chromosomally encoded actin proteins were found to play an important role in chromosome segregation. Based on the findings that actin filaments are dynamic structures in two bacterial species, we propose that actins perform motor functions rather than a purely structural role in bacteria. We suggest that an intracellular motor exists in bacteria that could be derived from an ancestral actin motor that was present in cells early in evolution.     

Interdisciplinary integration in biology? An overview

Philosophical theories about reduction and integration in science are at variance with what is happenign in science. A realistic approach to science show that possibilities for reduction and integration are limited. The classical ideal of a unified science has since long been rejected in philosophy. But the current emphasis on interdisciplinary integration in philosophy and in science shows that it survives in a different guise. It is necessary to redress the balance, specifically in biology. Methodological analysis shows that many of the grand interdisciplinary theories involving biology actually represent pseudo-integration covered up by inappropriate, overgeneral concepts. Integrationism is not bad, but it must be kept within reasonable bounds. If the present analysis is appropriate, there will have to be fundamental changes in research strategy both in science and in the philosophy of science.