Sex‐biased migration in humans: what should we expect from genetic data?

Different patterns of mitochondrial and Y-chromosome diversity have been cited as evidence of long-term patrilocality in human populations. However, what patterns are expected depends on the nature of the sampling scheme. Samples from a local region reveal only the recent demographic history of that region, whereas sampling over larger geographic scales accesses older demographic processes. A historical change in migration becomes evident first at local geographic scales, and alters global patterns of genetic diversity only after sufficient time has passed. Analysis of forager populations in the ethnographic record suggests that patrilocality may not have predominated among pre-agricultural humans. The higher female migration rate inferred by some genetic studies may reflect a shift to patrilocality in association with the emergence of agriculture. A recent global survey does not show the expected effects of higher female migration, possibly because the sampling scheme used for this study is accessing pre-agricultural human migration patterns. In this paper, we show how the demographic shift associated with agriculture might affect genetic diversity over different spatial scales. We also consider the prospects for studying sex-biased migration using the X-linked and autosomal markers. These multi-locus comparisons have the potential of providing more robust estimates of sex differences than Y-linked and mitochondrial data, but only if a very large number of loci are included in the analysis.     

Debate: When should we intervene in unstable angina - Time for an old look?

Current treatment modalities for patients with acute coronary syndromes center on early diagnosis, risk stratification and, increasingly, early treatment including invasive approaches. The appropriate timing of these invasive modalities in the context of the overall treatment program remains an area of controversy. Specifically, studies in the past recommended a period of medical 'stabilization' while current approaches are considerably more aggressive. The potential hazard of early intervention, in particular, has not properly been weighed against the benefit. This article hopes to provide a framework for examining the appropriate timing of intervention, specifically percutaneous coronary intervention, in acute coronary syndromes.     

Invasive trees and shrubs: where do they come from and what we should expect in the future?

The global database of invasive trees and shrubs has been updated, resulting in a total of 751 species (434 trees and 317 shrubs) from 90 families (Rejmánek and Richardson 2013 Divers Distrib 19:1093–1094). This database is used to assess major trends in human-assisted exchanges of dendrofloras among 15 major geographical regions. Areas most invaded by non-native trees are Pacific Islands (136 species), Southern Africa (118), Australia (116), and North America (114). Areas most invaded by non-native shrubs are North America (98), Australia (87), Pacific Islands (71), and Europe (61). The most important sources of invasive trees are Asia (122–146 species, depending on how many Eurasian species are considered to have been introduced only from Europe), Australia (81), and South America (81). The most important sources of invasive shrubs are Asia (103–118), Europe (68), and South America (54). Mean number of native geographical regions for invasive trees is 1.64, while the mean number of invaded regions by trees is 2.51. The difference is smaller for shrubs: 1.60 versus 2.11. Asia is the major source of invasive Rosaceae shrubs, as well as invasive Arecaceae and Oleaceae species. South America and Australia are major sources of invasive Fabaceae trees. North America and Europe are major sources of invasive Pinaceae. Most of the invasive Salicaceae are of Eurasian origin. The identified trends will very likely continue in this century. Because of increasing interactions with many states in Asia, even more invasive woody species will be introduced from this part of the world.     

Convergent evolution of gigantism in damselflies of Africa and South America? Evidence from nuclear and mitochondrial sequence data

Extreme large body size is rare in modern Zygoptera (damselflies). Only the South and Central American damselfly family Pseudostigmatidae and one African species, Coryphagrion grandis, share the morphological trait of gigantism. By means of phylogenetic analyses using two mitochondrial markers (16S rDNA and ND1) and one nuclear marker (EF1) in combination with an existing morphological data set, we trace the evolution of gigantism in damselflies. Individual and combined data sets were analyzed using the maximum parsimony, minimum evolution and maximum likelihood algorithms. Regardless of the algorithm used and the data set analyzed all principal tree topologies support a monophyly of the damselfly taxa displaying giant body size. This supports the view that the evolution of gigantism in damselflies from Africa and South America is not the result of convergent evolution due to strikingly similar habitat preferences, but rather the result of close genealogical relationship. Because modern odonates evolved before the split of Africa from Gondwanaland, the proposed phylogeny suggests that C. grandis represents a Gondwana relict.     

Homeostatic regulation upon changes of enzyme activities in the Calvin cycle as an example for general mechanisms of flux control. What can we expect from transgenic plants?

In order to explain the mechanisms of Calvin-cycle regulation, the general properties of metabolic systems under homeostatic flux control are analyzed. It is shown that the main characteristic point for an enzyme in such a system can be the value of a sharp transition from some constant homeostatic flux to a limitation by this enzyme. A special method for the quantitative treatment of the experimental dependence of a metabolic flux such as photosynthesis on enzyme content is developed. It is pointed out that reactions close to a thermodynamic equilibrium under normal conditions can considerably limit the homeostatic fluxes with a decrease of the enzyme content. Calvin-cycle enzymes are classified as non-limiting, near-limiting and limiting. The deduced rules for the regulation of a homeostatic metabolic pathway are used to explain the data obtained for transgenic plants with reduced activities of Calvin-cycle enzymes. The role of compensating mechanisms that maintain the photosynthesis rate constant upon the changes of enzyme contents is analyzed for the Calvin cycle. The developed analysis explains the sharp transitions between limiting and non-limiting conditions that can be seen in transgenic plants with reduced content of some Calvin-cycle enzymes, and the limiting role of such reversible enzymes as aldolase, transketolase and others. The attempt is made to predict the properties of plants with increased enzyme contents in the Calvin cycle.     

What have we learned from finite element model studies of lumbar intervertebral discs in the past four decades?

Finite element analysis is a powerful tool routinely used to study complex biological systems. For the last four decades, the lumbar intervertebral disc has been the focus of many such investigations. To understand the disc functional biomechanics, a precise knowledge of the disc mechanical, structural and biochemical environments at the microscopic and macroscopic levels is essential. In response to this need, finite element model studies have proven themselves as reliable and robust tools when combined with in vitro and in vivo measurements.     

Immunohistochemical analysis and 3D reconstruction of the cephalic nervous system in Chaetognatha: insights into the evolution of an early bilaterian brain?

Abstract. We examined the brain architecture in different species of Chaetognatha using immunofluorescence methods with a set of nervous system markers and confocal laser-scan microscopic analysis. These markers include antibodies against synaptic proteins, RFamide-related peptides, and tyrosinated tubulin, as well as a marker of cell nuclei. Furthermore, we present a 3D reconstruction based on histological section series. Our results expand the previous knowledge on neuroanatomy in Chaetognatha. We suggest a structural and functional subdivision of the rather complex chaetognath brain into two domains, a posterior domain that may be primarily involved in the integration of sensory input, and an anterior domain that may be involved in the control of the mouthparts and the anterior part of the digestive system. Immunolocalization of a neuropeptide suggests the presence of an identifiable group of neurons associated with the brain of all species examined here. However, our data also reveal a certain degree of interspecific variation and divergence within the Chaetognatha concerning, for example, the pattern of nerves branching off the brain and the proportional sizes of the various neuropil compartments. We compare our data to brain architecture in various other representatives of Protostomia and Deuterostomia. The chaetognath brain fits within the range of structural variation encountered in protostomian brains, and we cannot find any brain characteristics that would argue in favor of placing chaetognaths outside of the Protostomia. Rather, we see the circumoral arrangement of their cephalic nervous system as an argument that suggests protostome affinities.     

Is specialization an evolutionary dead end? Testing for differences in speciation,extinction and trait transition rates across diverse phylogenies of specialists and generalists

Specialization has often been claimed to be an evolutionary dead end, with specialist lineages having a reduced capacity to persist or diversify. In a phylogenetic comparative framework, an evolutionary dead end may be detectable from the phylogenetic distribution of specialists, if specialists rarely give rise to large, diverse clades. Previous phylogenetic studies of the influence of specialization on macroevolutionary processes have demonstrated a range of patterns, including examples where specialists have both higher and lower diversification rates than generalists, as well as examples where the rates of evolutionary transitions from generalists to specialists are higher, lower or equal to transitions from specialists to generalists. Here, we wish to ask whether these varied answers are due to the differences in macroevolutionary processes in different clades, or partly due to differences in methodology. We analysed ten phylogenies containing multiple independent origins of specialization and quantified the phylogenetic distribution of specialists by applying a common set of metrics to all datasets. We compared the tip branch lengths of specialists to generalists, the size of specialist clades arising from each evolutionary origin of a specialized trait and whether specialists tend to be clustered or scattered on phylogenies. For each of these measures, we compared the observed values to expectations under null models of trait evolution and expected outcomes under alternative macroevolutionary scenarios. We found that specialization is sometimes an evolutionary dead end: in two of the ten case studies (pollinator‐specific plants and host‐specific flies), specialization is associated with a reduced rate of diversification or trait persistence. However, in the majority of studies, we could not distinguish the observed phylogenetic distribution of specialists from null models in which specialization has no effect on diversification or trait persistence.     

How should we define fitness in structured metapopulation models? Including an application to the calculation of evolutionarily stable dispersal strategies

We define a fitness concept applicable to structured metapopulations consisting of infinitely many equally coupled patches. In addition, we introduce a more easily calculated quantity Rm that relates to fitness in the same manner as R0 relates to fitness in ordinary population dynamics: the Rm of a mutant is only defined when the resident population dynamics converges to a point equilibrium and Rm is larger (smaller) than 1 if and only if mutant fitness is positive (negative). Rm corresponds to the average number of newborn dispersers resulting from the (on average less than one) local colony founded by a newborn disperser. Efficient algorithms for calculating its numerical value are provided. As an example of the usefulness of these concepts we calculate the evolutionarily stable conditional dispersal strategy for individuals that can account for the local population density in their dispersal decisions. Below a threshold density x, at which staying and leaving are equality profitable, everybody should stay and above x everybody should leave, where profitability is measured as the mean number of dispersers produced through lines of descent consisting of non-dispersers.     

Unconstrained evolution in short introns? – An analysis of genome‐wide polymorphism and divergence data from Drosophila

An unconstrained reference sequence facilitates the detection of selection. In Drosophila, sequence variation in short introns seems to be least influenced by selection and dominated by mutation and drift. Here, we test this with genome‐wide sequences using an African population (Malawi) of D. melanogaster and data from the related outgroup species D. simulans, D. sechellia, D. erecta and D. yakuba. The distribution of mutations deviates from equilibrium, and the content of A and T (AT) nucleotides shows an excess of variance among introns. We explain this by a complex mutational pattern: a shift in mutational bias towards AT, leading to a slight nonequilibrium in base composition and context‐dependent mutation rates, with G or C (GC) sites mutating most frequently in AT‐rich introns. By comparing the corresponding allele frequency spectra of AT‐rich vs. GC‐rich introns, we can rule out the influence of directional selection or biased gene conversion on the mutational pattern. Compared with neutral equilibrium expectations, polymorphism spectra show an excess of low frequency and a paucity of intermediate frequency variants, irrespective of the direction of mutation. Combining the information from different outgroups with the polymorphism data and using a generalized linear model, we find evidence for shared ancestral polymorphism between D. melanogaster and D. simulans, D. sechellia, arguing against a bottleneck in D. melanogaster. Generally, we find that short introns can be used as a neutral reference on a genome‐wide level, if the spatially and temporally varying mutational pattern is accounted for.     

Is rat an appropriate animal model to study the involvement of D-serine catabolism in schizophrenia? Insights from characterization of D-amino acid oxidase

D-Amino acid oxidase (DAAO; EC1.4.3.3) has been proposed to play a main role in the degradation of D-serine, an allosteric activator of the N-methyl-D-aspartate-type glutamate receptor in the human brain, and to be associated with the onset of schizophrenia. To prevent excessive D-serine degradation, novel drugs for schizophrenia treatment based on DAAO inhibition were designed and tested on rats. However, the properties of rat DAAO are unknown and various in vivo trials have demonstrated the effects of DAAO inhibitors on d-serine concentration in rats. In the present study, rat DAAO was efficiently expressed in Escherichia coli. The recombinant enzyme was purified as an active, 40 kDa monomeric flavoenzyme showing the basic properties of the dehydrogenase-oxidase class of flavoproteins. Rat DAAO differs significantly from the human counterpart because: (a) it possesses a different substrate specificity; (b) it shows a lower kinetic efficiency, mainly as a result of a low substrate affinity; (c) it differs in affinity for the binding of classical inhibitors; (d) it is a stable monomer in the absence of an active site ligand; and (e) it interacts with the mammalian protein modulator pLG72 yielding a ~100 kDa complex in addition to the ~200 kDa one, as formed by the human DAAO. Furthermore, the concentration of endogenous D-serine in U87 glioblastoma cells was not affected by transfection with rat DAAO, whereas it was significantly decreased when expressing the human homologue. These results raise doubt on the use of the rat as a model system for testing new drugs against schizophrenia and indicate a different physiological function of DAAO in rodents and humans.     

Who should decide? Qualitative analysis of panel data from public,patients, healthcare professionals,and insurers on priorities in health care.

OBJECTIVE: To explore the arguments underlying the choices of patients, the public, general practitioners, specialists, and health insurers regarding priorities in health care. DESIGN: A qualitative analysis of data gathered in a series of panels. Members were asked to economise on the publicly funded healthcare budget, exemplified by 10 services. RESULTS: From a medical point of view, both panels of healthcare professionals thought most services were necessary. The general practitioners tried to achieve the budget cuts by limiting access to services to those most in need of them or those who cannot afford to pay for them. The specialists emphasised the possibilities of reducing costs by increasing the efficiency within services and preventing inappropriate utilisation. The patients mainly economised by limiting universal access to preventive and acute services. The "public" panels excluded services that are relatively inexpensive for individual patients. Moreover, they emphasised the individual''s own responsibility for health behaviour and the costs of health care, resulting in the choice for copayments. The health insurers emphasised the importance of including services that relate to a risk only, as well as feasibility aspects. CONCLUSIONS: There were substantial differences in the way the different groups approached the issue of what should be included in the basic package. Healthcare professionals seem to be most aware of the importance of maintaining equal access for everyone in need of health care.     

Why is grouper larval rearing difficult?: an approach from the development of the feeding apparatus in early stage larvae of the grouper,Epinephelus coioides

The osteological development of elements forming the oral cavity was examined in early stage larvae of the grouper,Epinephelus coioides, from hatching to 242.5 hours after hatching. By the time of initial mouth opening, at 54 hours after hatching, the fundamental elements, composed of the trabecula, some components of the lower branchial and hyoid arches, the quadrate and symplectic-hyomandibular cartilages, maxilla and Meckel's cartilage, had appeared. No further elements were observed until 165 hours after initial mouth opening, except some components in the lower branchial arch and head region. The appearance of new elements and initial ossification of existing cartilage occurred thereafter, but all elements related to feeding either had not appeared or had not started ossifying until 188.5 hours after initial mouth opening. Based on the morphology and developmental modes of these elements, the feeding mode of grouper larvae was considered to be “sucking/grasping.” However, the appearance and ossification of elements occurred slowly, with no transitional phase from sucking to grasping modes of feeding being observed during the study; such delayed development of the feeding-related bony elements was considered to be a cause of the difficulty in rearing early stage grouper larvae.