What is natural selection?

‘Natural selection’ is, it seems, an ambiguous term. It is sometimes held to denote a consequence of variation, heredity, and environment, while at other times as denoting a force that creates adaptations. I argue that the latter, the force interpretation, is a redundant notion of natural selection. I will point to difficulties in making sense of this linguistic practise, and argue that it is frequently at odds with standard interpretations of evolutionary theory. I provide examples to show this; one example involving the relation between adaptations and other traits, and a second involving the relation between selection and drift.     

Quantifying nanoscale biochemical heterogeneity in human epithelial cancer cells using combined AFM and PTIR absorption nanoimaging

Subcellular chemical heterogeneity plays a key role in cell organization and function. However the biomechanics underlying the structure‐function relationship is governed by cell substructures which are poorly resolved using conventional chemical imaging methods. To date, advances in sub‐diffraction limited infrared (IR) nanoscopy have permitted intracellular chemical mapping. In this work we report how image analysis applied to a combination of IR absorption nanoimaging and topographic data permits quantification of chemical complexity at the nanoscale, enabling the analysis of biochemical heterogeneity in mammalian cancer cells on the scale of subcellular features. (© 2013 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Effects of Cysteine Proteases on the Structural and Mechanical Properties of Collagen Fibers

Excessive cathepsin K (catK)-mediated turnover of fibrillar type I and II collagens in bone and cartilage leads to osteoporosis and osteoarthritis. However, little is known about how catK degrades compact collagen macromolecules. The present study is aimed to explore the structural and mechanical consequences of collagen fiber degradation by catK. Mouse tail type I collagen fibers were incubated with either catK or non-collagenase cathepsins. Methods used include scanning electron microscopy, protein electrophoresis, atomic force microscopy, and tensile strength testing. Our study revealed evidence of proteoglycan network degradation, followed by the progressive disassembly of macroscopic collagen fibers into primary structural elements by catK. Proteolytically released GAGs are involved in the generation of collagenolytically active catK-GAG complexes as shown by AFM. In addition to their structural disintegration, a decrease in the tensile properties of fibers was observed due to the action of catK. The Young''s moduli of untreated collagen fibers versus catK-treated fibers in dehydrated conditions were 3.2 ± 0.68 GPa and 1.9 ± 0.65 GPa, respectively. In contrast, cathepsin L, V, B, and S revealed no collagenase activity, except the disruption of proteoglycan-GAG interfibrillar bridges, which slightly decreased the tensile strength of fibers.     

Single molecule microscopy of biomembranes (Review)

Recent advances in the development of new microscopy techniques with a sensitivity of a single molecule have gained access to essentially new types of information obtainable from imaging biomolecular samples. These methodologies are analysed here in terms of their applicability to the in vivo visualization of cellular processes on the molecular scale, in particular of processes in cell membranes. First examples of single molecule microscopy on cell membranes revealed new basic insight into the lateral organization of the plasma membrane, providing the captivating perspective of an ultrasensitive methodology as a general tool to study local processes and heterogeneities in living cells.     

Understanding the kinetic roles of the inducer heparin and of rod-like protofibrils during amyloid fibril formation by Tau protein

The aggregation of the natively disordered protein, Tau, to form lesions called neurofibrillary tangles is a characteristic feature of several neurodegenerative tauopathies. The polyanion, heparin, is commonly used as an inducer in studies of Tau aggregation in vitro, but there is surprisingly no comprehensive model describing, quantitatively, all aspects of the heparin-induced aggregation reaction. In this study, rate constants and extents of fibril formation by the four repeat domain of Tau (Tau4RD) have been reproducibly determined over a full range of heparin and protein concentrations. The kinetic role of heparin in the nucleation-dependent fibril formation reaction is shown to be limited to participation in the initial rate-limiting steps; a single heparin molecule binds two Tau4RD molecules, forming an aggregation-competent protein dimer, which then serves as a building block for further fibril growth. Importantly, the minimal kinetic model that is proposed can quantitatively account for the characteristic bell-shaped dependence of the aggregation kinetics on the stoichiometry of protein to heparin. Very importantly, this study also identifies for the first time short and thin, rod-like protofibrils that are populated transiently, early during the time course of fibril formation. The identification of these protofibrils as bona fide off-pathway species has implications for the development of therapies for tauopathies based on driving fibril formation as a means of protecting the cell from smaller, putatively toxic aggregates.     

Spectrin-like repeats 11-15 of human dystrophin show adaptations to a lipidic environment

Dystrophin is essential to skeletal muscle function and confers resistance to the sarcolemma by interacting with cytoskeleton and membrane. In the present work, we characterized the behavior of dystrophin 11-15 (DYS R11-15), five spectrin-like repeats from the central domain of human dystrophin, with lipids. DYS R11-15 displays an amphiphilic character at the liquid/air interface while maintaining its secondary α-helical structure. The interaction of DYS R11-15 with small unilamellar vesicles (SUVs) depends on the lipid nature, which is not the case with large unilamellar vesicles (LUVs). In addition, switching from anionic SUVs to anionic LUVs suggests the lipid packing as a crucial factor for the interaction of protein and lipid. The monolayer model and the modulation of surface pressure aim to mimic the muscle at work (i.e. dynamic changes of muscle membrane during contraction and relaxation) (high and low surface pressure). Strikingly, the lateral pressure modifies the protein organization. Increasing the lateral pressure leads the proteins to be organized in a regular network. Nevertheless, a different protein conformation after its binding to monolayer is revealed by trypsin proteolysis. Label-free quantification by nano-LC/MS/MS allowed identification of the helices in repeats 12 and 13 involved in the interaction with anionic SUVs. These results, combined with our previous studies, indicate that DYS R11-15 constitutes the only part of dystrophin that interacts with anionic as well as zwitterionic lipids and adapts its interaction and organization depending on lipid packing and lipid nature. We provide strong experimental evidence for a physiological role of the central domain of dystrophin in sarcolemma scaffolding through modulation of lipid-protein interactions.     

Escape from predators and genetic variance in birds

Predation is a common cause of death in numerous organisms, and a host of antipredator defences have evolved. Such defences often have a genetic background as shown by significant heritability and microevolutionary responses towards weaker defences in the absence of predators. Flight initiation distance (FID) is the distance at which an individual animal takes flight when approached by a human, and hence, it reflects the life‐history compromise between risk of predation and the benefits of foraging. Here, we analysed FID in 128 species of birds in relation to three measures of genetic variation, band sharing coefficient for minisatellites, observed heterozygosity and inbreeding coefficient for microsatellites in order to test whether FID was positively correlated with genetic variation. We found consistently shorter FID for a given body size in the presence of high band sharing coefficients, low heterozygosity and high inbreeding coefficients in phylogenetic analyses after controlling statistically for potentially confounding variables. These findings imply that antipredator behaviour is related to genetic variance. We predict that many threatened species with low genetic variability will show reduced antipredator behaviour and that subsequent predator‐induced reductions in abundance may contribute to unfavourable population trends for such species.     

Foraging traits of native predators determine their vulnerability to a toxic alien prey

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Use of fragment–sharing estimates from DNA fingerprinting to determine relatedness in a tropical wren

We assessed the usefulness of DNA fragment–sharing scores from DNA fingerprints for assigning relatedness to unknown pairs of individuals in a population of stripe–backed wrens (Campylorhynchus nuchalis). Preliminary investigation of scoring biases revealed consistency both within and between scorers in relative band–sharing scores, but a tendency for scores to be inflated and for inter–scorer agreement to decline as distance between lanes on an autoradiograph increased. Distributions of band–sharing values matched expected distributions well, which suggests that variability in scores is mostly inherent and not a result of errors in scoring. Confidence intervals based on band–sharing scores or means of scores across enzymes, probes and scorers revealed that unrelated (r= 0) and first–order dyads (r=Vi) could be distinguished on the basis of single band–sharing scores from the best combination of enzyme and probe (HaeIII/33.15) and that first– and second–order dyads could be distinguished when confidence intervals were based on means of band–sharing scores across two enzymes, two probes and two scorers.     

A motion analysis marker-based method of determining centre of pressure during two-legged hopping

The fixed position of force plates has led researchers to pursue alternative methods of determining centre of pressure (CoP) location. To date, errors reported using alternative methods to the force plate during dynamic tasks have been high. The aim of this study was to investigate the accuracy of a motion analysis marker-based system to determine CoP during a two-legged hopping task. Five markers were attached to the left and right feet of eight healthy adults (5 females, 3 males, age: 25.0±2.8 years, height: 1.75±0.07 m, mass: 71.3±11.3 kg). Multivariate forward stepwise and forced entry linear regression was used with data from five participants to determine CoP position during quiet standing and hopping at various frequencies. Maximum standard error of the estimate of CoP position was 12 mm in the anteroposterior direction and 8 mm in the mediolateral. Cross-validation was performed using the remaining 3 participants. Maximum root mean square difference between the force plate and marker method was 14 mm for mediolateral CoP and 20 mm for anteroposterior CoP during 1.5 Hz hopping. Differences reduced to a maximum of 7 mm (mediolateral) and 14 mm (anteroposterior) for the other frequencies. The smallest difference in calculated sagittal plane ankle moment and timing of maximum moment was during 3.0 Hz hopping, and largest at 1.5 Hz. Results indicate the marker-based method of determining CoP may be a suitable alternative to a force plate to determine CoP position during a two-legged hopping task at frequencies greater than 1.5 Hz.