Temporal scaling of molecular evolution in primates and other mammals

Molecular clocks are routinely tested for linearity using a relative rate test and routinely calibrated against the geological time scale using a single or average paleontologically determined time of divergence between living taxa. The relative rate test is a test of parallel rate equality, not a test of rate constancy. Temporal scaling provides a test of rates, where scaling coefficients of 1.0 (isochrony) represent stochastic rate constancy. The fossil record of primates and other mammals is now known in sufficient detail to provide several independent divergence times for major taxonomic groups. Molecular difference should scale negatively or isochronically (scaling coefficients less than 1.0) with divergence time: where two or more divergence times are available, molecular difference appears to scale positively (scaling coefficient greater than 1.0). A minimum of four divergence times are required for adequate statistical power in testing the linear model: scaling is significantly nonlinear and positive in six of 11 published investigations meeting this criterion. All groups studied show some slowdown in rates of molecular change over Cenozoic time. The break from constant or increasing rates during the Mesozoic to decreasing rates during the Cenozoic appears to coincide with extraordinary diversification of placental mammals at the beginning of this era. High rates of selectively neutral molecular change may be concentrated in such discrete events of evolutionary diversification.      

Rethinking Motor Lateralization: Specialized but Complementary Mechanisms for Motor Control of Each Arm

Motor lateralization in humans has primarily been characterized as “handedness”, resulting in the view that one arm-hemisphere system is specialized for all aspects of movement while the other is simply a weaker analogue. We have proposed an alternative view that motor lateralization reflects proficiency of each arm for complementary functions that arises from a specialization of each hemisphere for distinct movement control mechanisms. However, before this idea of hemispheric specialization can be accepted, it is necessary to precisely identify these distinct, lateralized mechanisms. Here we show in right-handers that dominant arm movements rely on predictive mechanisms that anticipate and account for the dynamic properties of the arm, while the non-dominant arm optimizes positional stability by specifying impedance around equilibrium positions. In a targeted-reaching paradigm, we covertly and occasionally shifted the hand starting location either orthogonal to or collinear with a particular direction of movement. On trials on which the start positions were shifted orthogonally, we did not notice any strong interlimb differences. However, on trials on which start positions were shifted orthogonally, the dominant arm largely maintained the direction and straightness of its trajectory, while the non-dominant arm deviated towards the previously learned goal position, consistent with the hypothesized control specialization of each arm-hemisphere system. These results bring together two competing theories about mechanisms of movement control, and suggest that they coexist in the brain in different hemispheres. These findings also question the traditional view of handedness, because specialized mechanisms for each arm-hemisphere system were identified within a group of right-handers. It is likely that such hemispheric specialization emerged to accommodate increasing motor complexity during evolution.     

Short‐term insurance versus long‐term bet‐hedging strategies as adaptations to variable environments

Understanding how organisms adapt to environmental variation is a key challenge of biology. Central to this are bet‐hedging strategies that maximize geometric mean fitness across generations, either by being conservative or diversifying phenotypes. Theoretical models have identified environmental variation across generations with multiplicative fitness effects as driving the evolution of bet‐hedging. However, behavioral ecology has revealed adaptive responses to additive fitness effects of environmental variation within lifetimes, either through insurance or risk‐sensitive strategies. Here, we explore whether the effects of adaptive insurance interact with the evolution of bet‐hedging by varying the position and skew of both arithmetic and geometric mean fitness functions. We find that insurance causes the optimal phenotype to shift from the peak to down the less steeply decreasing side of the fitness function, and that conservative bet‐hedging produces an additional shift on top of this, which decreases as adaptive phenotypic variation from diversifying bet‐hedging increases. When diversifying bet‐hedging is not an option, environmental canalization to reduce phenotypic variation is almost always favored, except where the tails of the fitness function are steeply convex and produce a novel risk‐sensitive increase in phenotypic variance akin to diversifying bet‐hedging. Importantly, using skewed fitness functions, we provide the first model that explicitly addresses how conservative and diversifying bet‐hedging strategies might coexist.     

Designing adverse event forms for real-world reporting: participatory research in Uganda

The wide-scale roll-out of artemisinin combination therapies (ACTs) for the treatment of malaria should be accompanied by continued surveillance of their safety. Post-marketing pharmacovigilance (PV) relies on adverse event (AE) reporting by clinicians, but as a large proportion of treatments are provided by non-clinicians in low-resource settings, the effectiveness of such PV systems is limited. To facilitate reporting, AE forms should be easily completed; however, most are challenging for lower-level health workers and non-clinicians to complete. Through participatory research, we sought to develop user-friendly AE report forms to capture information on events associated with ACTs.Following situation analysis, we undertook workshops with community medicine distributors and health workers in Jinja, Uganda, to develop a reporting form based on experiences and needs of users, and communication and visual perception principles. Participants gave feedback for revisions of subsequent versions. We then conducted 8 pretesting sessions with 77 potential end users to test and refine passive and active versions of the form.The development process resulted in a form that included a pictorial storyboard to communicate the rationale for the information needed and facilitate rapport between the reporter and the respondent, and a diary format to record the drug administration and event details in chronological relation to each other. Successive rounds of pretesting used qualitative and quantitative feedback to refine the form, with the final round showing over 80% of the form completed correctly by potential end users.We developed novel AE report forms that can be used by non-clinicians to capture pharmacovigilance data for anti-malarial drugs. The participatory approach was effective for developing forms that are intuitive for reporters, and motivating for respondents. The forms, or their key components, could be adapted for use in other low-literacy settings to improve quality and quantity of drug safety reports as new medicines are scaled-up.     

Wasserlinsen als Nutzpflanzen

Duckweeds as crop plants Members of the plant family Lemnaceae (duckweeds) are not only interesting because they represent the smallest flowering plants; they possess also the fastest rates of producing biomass. As aquatic plants, duckweed production is not in competition with other agricultural crops that require fertile land while the cultivation of duckweeds does not contribute to further eutrophication of surface water. Instead, they can be cultivated on municipal or agricultural waste water and remove the nutrients during their propagation and growth. Duckweeds can thus be used for cleaning of waste water and the resulting biomass can be valuable starting material for animal feeds and the production of biofuels. Research focusing on these goals has begun to transfer from research laboratories to pilot plants in different parts of the world, e.g. in New Jersey and North Carolina, USA; Chengdu, P. R. China; and Armidale, Australia.     

Myotone Dystrophien – und ihre Differenzialdiagnosen

The classic myotonic dystrophy, Steinert’s disease (DM1) was first described in 1909, and the second type, Ricker’s disease (DM2), in 1994. In 1992 the disease-causing mutation in DM1 was identified as a CTG repeat in the DMPK gene on chromosome 19q, and in 2001 the DM2 mutation was identified as a CCTG repeat expansion in the ZNF9 gene on chromosome 3q. Multisystemic symptoms of the diseases affect skeletal muscle, brain, eye, heart, and the endocrine system. The pathogenesis of both forms seems to be based on a gain-of-function RNA mechanism and on alterations in RNA metabolism and spliceopathy. Our review focuses on clinical features, diagnostic techniques, and new aspects of molecular pathogenesis and therapy.     

Genetik der monogenen isolierten Alopezien

The monogenic inherited isolated alopecias comprise a group of clinically and genetically heterogeneous forms of hairlessness or hair loss. Clinical classification of the isolated alopecias is based on the onset of the disorder, the regions affected, and the structure of the hair shaft. Men and women are equally affected, and the mode of inheritance is autosomal dominant or autosomal recessive. Since the identification of the keratin gene KRT86 as a cause of the so-called monilethrix in 1997, mutations in nine other genes have been identified for various isolated alopecias. These include other keratin genes for monilethrix (KRT81 and KRT83), the hairless gene for atrichia congenita/papular atrichia, the corneodesmosin gene for the autosomal dominant form of hypotrichosis simplex, and the genes desmoglein 4, lipase H, and the G-protein-coupled receptor P2RY5 (LPAR6) for the autosomal recessive forms of hypotrichosis. Molecular genetic and pathophysiological studies of these rare disorders of hair development have contributed significantly to our understanding of the basic mechanisms of hair loss as well as the physiological mechanisms of hair growth.