What sets the long-term level of sympathetic nerve activity: is there a role for arterial baroreceptors?

Much of our knowledge of the influence of the sympathetic nervous system on the control of blood pressure is built on experimental approaches that focus very much on time scales <24 h. Although direct recordings of sympathetic nerve activity (SNA) over short time scales provide important information, it is difficult to place their relevance over the longer term where the development of chronic changes in blood pressure are likely to be a mixture of hormonal, renal, and neural influences. Recently new experimental approaches are now revealing a possible role for arterial baroreceptors in the chronic regulation of SNA. These studies reveal that chronic increases in blood pressure are associated with chronic changes in SNA that may be due to nonresetting of the blood pressure-SNA baroreflex relationship. This review discusses the implications of such information, highlighting new technologies for long-term recording of SNA that appear to hold much promise for revealing the role of SNA to the kidney for the long-term control of blood pressure.     

What are the implications of evolvable molecules?

James Shapiro’s view of evolution is inspired by looking at the molecular mechanisms of mutation. Finding these systems to be intelligent and the mutations non-gradual, Shapiro concludes that neither the role of DNA in development, nor and the role of natural selection in evolution are what we thought them to be. The cases discussed are interesting and may require some modification of theory in biology, but this reviewer finds many of Shapiro’s conclusions unwarranted.     

What are the baselines for protein fold recognition?

MOTIVATION: What constitutes a baseline level of success for protein fold recognition methods? As fold recognition benchmarks are often presented without any thought to the results that might be expected from a purely random set of predictions, an analysis of fold recognition baselines is long overdue. Given varying amounts of basic information about a protein-ranging from the length of the sequence to a knowledge of its secondary structure-to what extent can the fold be determined by intelligent guesswork? Can simple methods that make use of secondary structure information assign folds more accurately than purely random methods and could these methods be used to construct viable hierarchical classifications? EXPERIMENTS PERFORMED: A number of rapid automatic methods which score similarities between protein domains were devised and tested. These methods ranged from those that incorporated no secondary structure information, such as measuring absolute differences in sequence lengths, to more complex alignments of secondary structure elements. Each method was assessed for accuracy by comparison with the Class Architecture Topology Homology (CATH) classification. Methods were rated against both a random baseline fold assignment method as a lower control and FSSP as an upper control. Similarity trees were constructed in order to evaluate the accuracy of optimum methods at producing a classification of structure. RESULTS: Using a rigorous comparison of methods with CATH, the random fold assignment method set a lower baseline of 11% true positives allowing for 3% false positives and FSSP set an upper benchmark of 47% true positives at 3% false positives. The optimum secondary structure alignment method used here achieved 27% true positives at 3% false positives. Using a less rigorous Critical Assessment of Structure Prediction (CASP)-like sensitivity measurement the random assignment achieved 6%, FSSP-59% and the optimum secondary structure alignment method-32%. Similarity trees produced by the optimum method illustrate that these methods cannot be used alone to produce a viable protein structural classification system. CONCLUSIONS: Simple methods that use perfect secondary structure information to assign folds cannot produce an accurate protein taxonomy, however they do provide useful baselines for fold recognition. In terms of a typical CASP assessment our results suggest that approximately 6% of targets with folds in the databases could be assigned correctly by randomly guessing, and as many as 32% could be recognised by trivial secondary structure comparison methods, given knowledge of their correct secondary structures.     

What are the relevant parameters for the geometrical optimization of an implantable bioartificial pancreas?

A sphere within a cylinder representing the islet encapsulated in a hollow fiber can model an implantable bioartificial pancreas. Based on a finite element model for insulin response to a glucose load in the presence of various oxygen supplies, the present study aimed at pointing out the major parameters influencing this secretion. The computational results treated with the Taguchi method clearly demonstrated that geometrical parameters (fiber length and islet density) should be precisely optimized for an enhanced insulin response. This requires the collection of more relevant experimental data concerning the islet oxygen consumption. Moreover, the relative errors on glucose consumption or insulin secretion by the islets do not seem to affect the whole optimization process, which should focus on the oxygen supply to islets.     

What are the organismic elements of vegetation science?

The recent inclusion of communities of planktonic algae and microbial crusts into the system of European vegetation types is critically discussed. It is argued that formal vegetation classification should be limited to plant taxa represented by macroscopic individuals within a plot, including all vascular plants, bryophytes, lichens, charophyta and macrophytic chlorophyta, rhodophyta or phaeophyta. In the interest of comparability and methodological stringency, all microscopic algae and all prokaryotes, including cyanobacteria, and the habitats dominated by such microorganisms (e.g. plankton, biofilms and crusts), should be excluded from vegetation classification.     

What are the consequences of being left-clawed in a predominantly right-clawed fiddler crab?

Male fiddler crabs (genus Uca) have an enlarged major claw that is used during fights. In most species, 50% of males have a major claw on the left and 50% on the right. In Uca vocans vomeris, however, less than 1.4% of males are left-clawed. Fights between opponents with claws on the same or opposite side result in different physical alignment of claws, which affects fighting tactics. Left-clawed males mainly fight opposite-clawed opponents, so we predicted that they would be better fighters due to their relatively greater experience in fighting opposite-clawed opponents. We found, however, that (i) a left-clawed male retains a burrow for a significantly shorter period than a size-matched right-clawed male, (ii) when experimentally displaced from their burrow, there is no difference in the tactics used by left- and right-clawed males to obtain a new burrow; however, right-clawed males are significantly more likely to initiate fights with resident males, and (iii) right-clawed residents engage in significantly more fights than left-clawed residents. It appears that left-clawed males are actually less likely to fight, and when they do fight they are less likely to win, than right-clawed males. The low-level persistence of left-clawed males is therefore unlikely to involve a frequency-dependent advantage associated with fighting experience.     

What are the genomic drivers of the rapid evolution of PRDM9?

Mammalian Prdm9 has been proposed to be a key determinant of the positioning of chromosome double-strand breaks during meiosis, a contributor to speciation processes, and the most rapidly evolving gene in human, and other animal, genomes. Prdm9 genes often exhibit substantial variation in their numbers of encoded zinc fingers (ZFs), not only between closely related species but also among individuals of a species. The near-identity of these ZF sequences appears to render them very unstable in copy number. The rare sequence differences, however, cluster within ZF sites that determine the DNA-binding specificity of PRDM9, and these substitutions are frequently positively selected. Here, possible drivers of the rapid evolution of Prdm9 are discussed, including selection for efficient pairing of homologous chromosomes or for recombination of deleterious linked alleles, and selection against depletion of recombination hotspots or against disease-associated genome rearrangement.     

What are the immunological consequences of long-term use of biological therapies for juvenile idiopathic arthritis?

This review summarizes the immunological consequences of biological therapies used in juvenile idiopathic arthritis (JIA). For every frequently used biological agent the characteristics are clearly specified (molecular target, isotype, registered indication for JIA, route of administration, half-life, contraindication, very common side effects, expected time of response and average cost in the first year). The emphasis of this review is on the immunological side effects that have been encountered for every separate agent in JIA populations. For each agent these adverse events have been calculated as incidence per 100 patient-years for the following categories: serious infections, tuberculosis, malignancies, response to vaccination, new-onset autoimmune diseases and development of anti-drug antibodies. There are large differences in side effects between various agents and there is a clear need for an international and standardized collection of post-marketing surveillance data of biologicals in the vulnerable group of JIA patients. Such an international pharmacovigilance database, called Pharmachild, has now been started.