How, when and why proteins collapse: the relation to folding

Unfolded proteins under strongly denaturing conditions are highly expanded. However, when the conditions are more close to native, an unfolded protein may collapse to a compact globular structure distinct from the folded state. This transition is akin to the coil-globule transition of homopolymers. Single-molecule FRET experiments have been particularly conducive in revealing the collapsed state under conditions of coexistence with the folded state. The collapse can be even more readily observed in natively unfolded proteins. Time-resolved studies, using FRET and small-angle scattering, have shown that the collapse transition is a very fast event, probably occurring on the submicrosecond time scale. The forces driving collapse are likely to involve both hydrophobic and backbone interactions. The loss of configurational entropy during collapse makes the unfolded state less stable compared to the folded state, thus facilitating folding.     

How to distinguish altruism from spite (and why we should bother)

Social behaviour is often described as altruistic, spiteful, selfish or mutually beneficial. These terms are appealing, but it has not always been clear how they are defined and what purpose they serve. Here, I show that the distinctions among them arise from the ways in which fitness is partitioned: none can be drawn when the fitness consequences of an action are wholly aggregated, but they manifest clearly when the consequences are partitioned into primary and secondary (neighbourhood) effects. I argue that the primary interaction is the principal source of adaptive design, because (i) it is this interaction that determines the fit of an adaptation and (ii) it is the actor and primary recipients whom an adaptation foremost affects. The categories of social action are thus instrumental to any account of evolved function.     

From Carrel to Hayflick and back, or what we got from the 100-year cytogerontological studies

The history of gerontological experiments on cell cultures is reviewed. Cytogerontological studies and aging theories by Weismann, Carrel, Hayflick, and the author are compared. It is emphasized that the basic notion of aging mechanisms was deeply revised several times within the 20th century. It is concluded that at present the aging of multicellular organisms cannot be satisfactorily explained with the help of cytogerontological studie’s data. Experiments on cell cultures need to be combined with fundamental gerontological studies, including survival curve analysis for humans or experimental animals.     

Intestinal "bioavailability" of solutes and water: we know how but not why.

Only minimal quantities of ingested and normally secreted solutes and water are excreted in the stool. This near 100% bioavailability means that the diet and kidneys are relatively more important determinants of solute, water and acid-base balance than the intestine. Intestinal bioavailability is based on excess transport capacity under normal conditions and the ability to adapt to altered or abnormal conditions. Indeed, the regulatory system of the intestine is as complex, segmented and multi factorial as in the kidney. Alterations in the rate and intestinal site of absorption reflect this regulation, and the diagnosis and treatment of various clinical abnormalities depend on the integrity of intestinal absorptive processes. However, the basis for this regulation an bioavailability are uncertain. Perhaps they had survival value for mammals, a phylogenic class that faced the twin threats of intestinal pathogens and shortages of solutes and water.     

From "butyribacterium" to "E. coli": an essay on unity in biochemistry

New ideas in science frequently arise from neglected or distorted antecedents. This essay deals with the idea of biochemical unity, encapsulated in Jacques Monod's well-known phrase, dating from 1954: "Anything found to be true of E. coli must also be true of elephants." An earlier version of this phrase,--"From the elephant to butyric acid bacterium--it is all the same!"--was coined in 1926 by the Dutch microbiologist Albert Jan Kluyver. In that year Kluyver and his associate Hendrick Jean Louis Donker published a celebrated paper, "Unity in Biochemistry." The concept of biochemical unity had many antecedents, but these had never caught on. The Kluyver-Donker paper has often been regarded to provide a boost to biochemical and especially to microbiological thinking. Its interpretations and misinterpretations represent an encapsulated history of biochemistry. The present paper examines the history of the concept of biochemical unity from before to beyond Kluyver, investigates the two "elephant" phrases and their possible relationships, and ends with a discussion of the attractiveness of unifying ideas in science.     

"遗传与进化"模块中"假说-演绎法"的教学

“假说-演绎法”是高中生物课程标准在“遗传与进化”模块对高中学生提出的科学方法的要求,许多教师对假说演绎的内涵感到陌生,对其教学的落实更加困惑,因而在新课程的教学中出现忽略“假说-演绎法”的教学或者教学不到位的现象。阐述了“假说-演绎法”的含义,“假说-演绎法”在自然科学发展中的重要作用,介绍了“遗传与进化”模块中适用“假说-演绎法”教学的素材,对可供教学的典型案例做了剖析,并提出了教学建议。     

How to predict diffusion of medium-sized molecules in polymer matrices. From atomistic to coarse grain simulations

The normal diffusion regime of many small and medium-sized molecules occurs on a time scale that is too long to be studied by atomistic simulations. Coarse-grained (CG) molecular simulations allow to investigate length and time scales that are orders of magnitude larger compared to classical molecular dynamics simulations, hence providing a valuable approach to span time and length scales where normal diffusion occurs. Here we develop a novel multi-scale method for the prediction of diffusivity in polymer matrices which combines classical and CG molecular simulations. We applied an atomistic-based method in order to parameterize the CG MARTINI force field, providing an extension for the study of diffusion behavior of penetrant molecules in polymer matrices. As a case study, we found the parameters for benzene (as medium sized penetrant molecule whose diffusivity cannot be determined through atomistic models) and Poly (vinyl alcohol) (PVA) as polymer matrix. We validated our extended MARTINI force field determining the self diffusion coefficient of benzene (2.27·10⁻⁹ m² s⁻¹) and the diffusion coefficient of benzene in PVA (0.263·10⁻¹² m² s⁻¹). The obtained diffusion coefficients are in remarkable agreement with experimental data (2.20·10⁻⁹ m² s⁻¹ and 0.25·10⁻¹² m² s⁻¹, respectively). We believe that this method can extend the application range of computational modeling, providing modeling tools to study the diffusion of larger molecules and complex polymeric materials.     

"They want to know where they came from": population genetics, identity, and family genealogy

This paper discusses the changing relationship between population genetics, family genealogy and identity. It reports on empirical research with participants in a genetic study who anticipated that personal feedback on the analysis of their donated samples would elucidate aspects of their own family genealogies. The paper also documents how geneticists, building on the practices of offering personal feedback to research participants, have developed genetic tests marketed directly to people wishing to trace their ancestry. Some of the social and ethical issues raised by this development in the use of genetic testing are considered.     

From beta-lipotropin to beta-endorphin and 'pro-opio-melanocortin'.

Studies on the biosynthesis of beta-LPH on the one hand, and of ACTH on the other, have produced a new concept, that of a single precursor form which contains three active molecules. Thus, it is proper to name such a precursor 'pro-opio-melanocortin.' The concept that beta-LPH was a precursor molecule was first put forward in 1967 and was based on both structural forms and biological activities. The discovery that morphine-like substances are part of the C-terminal fragment of beta-LPH brought an additional important biological side product. That, together with the recent demonstration of ACTH as part of a still larger precursor, constitutes an exciting model for the study of peptide hormone biosynthesis. We have shown unambiguously that beta-endorphin is the result of a maturation process from the large precursor, while beta-LPH is an important and transient intermediary. Since it is also present in the brain, our recent results using pars intermedia cells can be applied to study the fabrication and degradation of these molecules in the brain. We expect to see it established that all other neuropeptides are also biosynthesized as larger precursor molecules whose structure at the site of cleavage could well be constituted of two basic amino acids like in the pro-opio-melanocortin.