Distribution of the Character States “Early Sympetaly” and “Late Sympetaly” Within the “Sympetalae Tetracyclicae” and Presumably Allied Groups*

Within the Asteridae (“Sympetalae Tetracyclicae”) two main developmental patterns can be distinguished as regards the formation of corolla tubes, namely “early” and “late sympetaly”. Since the character “ontogeny of sympetaly”, after intensive studies, proved to be valuable for systematic considerations, we now recognize two blocks of orders within the Asteridae (and related groups): the Asteridae A-block and the Asteridae B-block (Figs. 82 and 83). By and large this bipartition referring mainly to the corolla tube development corresponds well with major lineages indentified by recent molecular data (see, e.g., Chase et al., 1993). Asteridae A-block is characterized predominantely by “late sympetaly” the “early sympetaly” in Rubiales and Oleales can be interpreted as derived within this block or can be linked with that in Asteridae B-block. Asteridae B-block is uniform throughout in its “early sympetaly”. In this block it is a primitive character, as judged from its occasional occurrence in the choripetalous Cornales and Apiales (Apiaceae, Araliaceae, Pittosporaceae), which can be regarded as ancestral for block B.     

Accurate geometries for “Mountain pass” regions of the Ramachandran plot using quantum chemical calculations

Unusual local arrangements of protein in Ramachandran space are not well represented by standard geometry tools used in either protein structure refinement using simple harmonic geometry restraints or in protein simulations using molecular mechanics force fields. In contrast, quantum chemical computations using small poly‐peptide molecular models can predict accurate geometries for any well‐defined backbone Ramachandran orientation. For conformations along transition regions—ϕ from −60 to 60°—a very good agreement with representative high‐resolution experimental X‐ray (≤1.5 Å) protein structures is obtained for both backbone C⁻¹‐N‐C_α angle and the nonbonded O⁻¹…C distance, while “standard geometry” leads to the “clashing” of O…C atoms and Amber FF99SB predicts distances too large by about 0.15 Å. These results confirm that quantum chemistry computations add valuable support for detailed analysis of local structural arrangements in proteins, providing improved or missing data for less understood high‐energy or unusual regions.     

Transcriptome analysis reveals the difference between “healthy” and “common” aging and their connection with age‐related diseases

A key goal of aging research was to understand mechanisms underlying healthy aging and develop methods to promote the human healthspan. One approach is to identify gene regulations unique to healthy aging compared with aging in the general population (i.e., “common” aging). Here, we leveraged Genotype‐Tissue Expression (GTEx) project data to investigate “healthy” and “common” aging gene expression regulations at a tissue level in humans and their interconnection with diseases. Using GTEx donors' disease annotations, we defined a “healthy” aging cohort for each tissue. We then compared the age‐associated genes derived from this cohort with age‐associated genes from the “common” aging cohort which included all GTEx donors; we also compared the “healthy” and “common” aging gene expressions with various disease‐associated gene expressions to elucidate the relationships among “healthy,” “common” aging and disease. Our analyses showed that 1. GTEx “healthy” and “common” aging shared a large number of gene regulations; 2. Despite the substantial commonality, “healthy” and “common” aging genes also showed distinct function enrichment, and “common” aging genes had a higher enrichment for disease genes; 3. Disease‐associated gene regulations were overall different from aging gene regulations. However, for genes regulated by both, their regulation directions were largely consistent, implying some aging processes could increase the susceptibility to disease development; and 4. Possible protective mechanisms were associated with some “healthy” aging gene regulations. In summary, our work highlights several unique features of GTEx “healthy” aging program. This new knowledge could potentially be used to develop interventions to promote the human healthspan.     

“How” and “what” matters: Sampling method affects biodiversity estimates of reef fishes

Understanding changes in biodiversity requires the implementation of monitoring programs encompassing different dimensions of biodiversity through varying sampling techniques. In this work, fish assemblages associated with the “outer” and “inner” sides of four marinas, two at the Canary Islands and two at southern Portugal, were investigated using three complementary sampling techniques: underwater visual censuses (UVCs), baited cameras (BCs), and fish traps (FTs). We firstly investigated the complementarity of these sampling methods to describe species composition. Then, we investigated differences in taxonomic (TD), phylogenetic (PD) and functional diversity (FD) between sides of the marinas according to each sampling method. Finally, we explored the applicability/reproducibility of each sampling technique to characterize fish assemblages according to these metrics of diversity. UVCs and BCs provided complementary information, in terms of the number and abundances of species, while FTs sampled a particular assemblage. Patterns of TD, PD, and FD between sides of the marinas varied depending on the sampling method. UVC was the most cost‐efficient technique, in terms of personnel hours, and it is recommended for local studies. However, for large‐scale studies, BCs are recommended, as it covers greater spatio‐temporal scales by a lower cost. Our study highlights the need to implement complementary sampling techniques to monitor ecological change, at various dimensions of biodiversity. The results presented here will be useful for optimizing future monitoring programs.     

Toward a “Structural BLAST”: Using structural relationships to infer function

We outline a set of strategies to infer protein function from structure. The overall approach depends on extensive use of homology modeling, the exploitation of a wide range of global and local geometric relationships between protein structures and the use of machine learning techniques. The combination of modeling with broad searches of protein structure space defines a “structural BLAST” approach to infer function with high genomic coverage. Applications are described to the prediction of protein–protein and protein–ligand interactions. In the context of protein–protein interactions, our structure‐based prediction algorithm, PrePPI, has comparable accuracy to high‐throughput experiments. An essential feature of PrePPI involves the use of Bayesian methods to combine structure‐derived information with non‐structural evidence (e.g. co‐expression) to assign a likelihood for each predicted interaction. This, combined with a structural BLAST approach significantly expands the range of applications of protein structure in the annotation of protein function, including systems level biological applications where it has previously played little role.     

What are genes “for” or where are traits “from”? What is the question?

For at least a century it has been known that multiple factors play a role in the development of complex traits, and yet the notion that there are genes “for” such traits, which traces back to Mendel, is still widespread. In this paper, we illustrate how the Mendelian model has tacitly encouraged the idea that we can explain complexity by reducing it to enumerable genes. By this approach many genes associated with simple as well as complex traits have been identified. But the genetic architecture of biological traits, or how they are made, remains largely unknown. In essence, this reflects the tension between reductionism as the current “modus operandi” of science, and the emerging knowledge of the nature of complex traits. Recent interest in systems biology as a unifying approach indicates a reawakened acceptance of the complexity of complex traits, though the temptation is to replace “gene for” thinking by comparably reductionistic “network for” concepts. Both approaches implicitly mix concepts of variants and invariants in genetics. Even the basic question is unclear: what does one need to know to “understand” the genetic basis of complex traits? New operational ideas about how to deal with biological complexity are needed.     

THE EVOLUTION OF PHENOTYPIC CORRELATIONS AND “DEVELOPMENTAL MEMORY”

Development introduces structured correlations among traits that may constrain or bias the distribution of phenotypes produced. Moreover, when suitable heritable variation exists, natural selection may alter such constraints and correlations, affecting the phenotypic variation available to subsequent selection. However, exactly how the distribution of phenotypes produced by complex developmental systems can be shaped by past selective environments is poorly understood. Here we investigate the evolution of a network of recurrent nonlinear ontogenetic interactions, such as a gene regulation network, in various selective scenarios. We find that evolved networks of this type can exhibit several phenomena that are familiar in cognitive learning systems. These include formation of a distributed associative memory that can “store” and “recall” multiple phenotypes that have been selected in the past, recreate complete adult phenotypic patterns accurately from partial or corrupted embryonic phenotypes, and “generalize” (by exploiting evolved developmental modules) to produce new combinations of phenotypic features. We show that these surprising behaviors follow from an equivalence between the action of natural selection on phenotypic correlations and associative learning, well‐understood in the context of neural networks. This helps to explain how development facilitates the evolution of high‐fitness phenotypes and how this ability changes over evolutionary time.     

A critique of the “ultra‐high risk” and “transition” paradigm

The transdiagnostic expression of psychotic experiences in common mental disorder (anxiety/depression/substance use disorder) is associated with a poorer prognosis, and a small minority of people may indeed develop a clinical picture that meets criteria for schizophrenia. However, it appears neither useful nor valid to observe early states of multidimensional psychopathology in young people through the “schizo”‐prism, and apply misleadingly simple, unnecessary and inefficient binary concepts of “risk” and “transition”. A review of the “ultra‐high risk” (UHR) or “clinical high risk” (CHR) literature indicates that UHR/CHR samples are highly heterogeneous and represent individuals diagnosed with common mental disorder (anxiety/depression/substance use disorder) and a degree of psychotic experiences. Epidemiological research has shown that psychotic experiences are a (possibly non‐causal) marker of the severity of multidimensional psychopathology, driving poor outcome, yet notions of “risk” and “transition” in UHR/CHR research are restrictively defined on the basis of positive psychotic phenomena alone, ignoring how baseline differences in multidimensional psychopathology may differentially impact course and outcome. The concepts of “risk” and “transition” in UHR/CHR research are measured on the same dimensional scale, yet are used to produce artificial diagnostic shifts. In fact, “transition” in UHR/CHR research occurs mainly as a function of variable sample enrichment strategies rather than the UHR/CHR “criteria” themselves. Furthermore, transition rates in UHR/CHR research are inflated as they do not exclude false positives associated with the natural fluctuation of dimensional expression of psychosis. Biological associations with “transition” thus likely represent false positive findings, as was the initial claim of strong effects of omega‐3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR intervention research has focused on the questionable outcome of “transition”, which shows lack of correlation with functional outcome. It may be more productive to consider the full range of person‐specific psychopathology in all young individuals who seek help for mental health problems, instead of “policing” youngsters for the transdiagnostic dimension of psychosis. Instead of the relatively inefficient medical high‐risk approach, a public health perspective, focusing on improved access to a low‐stigma, high‐hope, small scale and youth‐specific environment with acceptable language and interventions may represent a more useful and efficient strategy.     

Dietary Restraint and Control Over “Wanting” Following Consumption of “Forbidden” Food

Eating behavior can be influenced by the rewarding value of food, i.e., “liking” and “wanting.” The objective of this study was to assess in normal‐weight dietary restrained (NR) vs. unrestrained (NU) eaters how rewarding value of food is affected by satiety, and by eating a nonhealthy perceived, dessert‐specific food vs. a healthy perceived, neutral food (chocolate mousse vs. cottage cheese). Subjects (24NR age = 25.0 ± 8.2 years, BMI = 22.3 ± 2.1 kg/m²; 26NU age = 24.8 ± 8.0 years, BMI = 22.1 ± 1.7 kg/m²) came to the university twice, fasted (randomized crossover design). Per test‐session “liking” and “wanting” for 72 items divided in six categories (bread, filling, drinks, dessert, sweets, stationery (placebo)) was measured, before and after consumption of chocolate mousse/cottage cheese, matched for energy content (5.6 kJ/g) and individual daily energy requirements (10%). Chocolate mousse was liked more than cottage cheese (P < 0.05). After consumption of chocolate mousse or cottage cheese, appetite and “liking” vs. placebo were decreased in NR and NU (P < 0.03), whereas “wanting” was only decreased in NR vs. NU (P ≤ 0.01). In NR vs. NU “wanting” was specifically decreased after chocolate mousse vs. cottage cheese; this decrease concerned especially “wanting” for bread and filling (P < 0.05). To conclude, despite similar decreases in appetite and “liking” after a meal in NR and NU, NR decrease “wanting” in contrast to NU. NR decrease “wanting” specifically for a nonhealthy perceived, “delicious,” dessert‐specific food vs. a nutritional identical, yet healthy perceived, slightly less “delicious,” “neutral” food. A healthy perceived food may thus impose greater risk for control of energy intake in NR.     

150 Jahre “Biogenetisches Grundgesetz”

150 years “Biogenetic Law” The zoologist Ernst Haeckel is one of the most well‐known, but also one of the most controversial scientists of the late 19th and early 20th centuries. He was one of the earliest Darwinists and a forceful advocate of evolutionary theory. Together with “Darwin's Bulldog” Thomas Henry Huxley, Haeckel was a central figure in the early history and popularization of Darwinism. But his name is not only a symbol for the disputes about the theory of evolution and its popularization, but also for a campaign for monism, a world‐view or philosophy created by Haeckel himself. Together with Fritz Müller, Ernst Haeckel was one of the first to formulate a “Biogenetic Law”. He also created several concepts and terms still in use in biology today, such as “ontogeny”, “phylogeny”, “ecology”, “cholorogy” and “phylum” in his first, and maybe most important book “General Morphology of Organism”, which was published in 1866, 150 years ago.     

Tumor microenvironment as the “regulator” and “target” for gene therapy

In this review, we focus on strategies for designing functional nano gene carriers, as well as choosing therapeutic genes targeting the tumor microenvironment. Gene mutations have a great impact on the occurrence of cancer. Thus, gene therapy plays a major role in cancer therapy and has the potential to cure cancer. Well‐designed gene therapy largely relies on effective gene carriers, which can be divided into viral carriers and non‐viral carriers. A gene carrier delivers functional genes to their intracellular target and avoids nucleic acids being degraded by nucleases in the serum. Most conventional cancer gene therapies only target cancer cells and do not appear to be sufficintly efficient to pass clinical trials. Accumulating evidence has shown that extending the therapeutic strategies to the tumor microenvironment, rather than the tumor cell itself, can allow more options for achieving robust anti‐cancer efficiency. In addition, unusual features between tumor microenvironment and normal tissues, such as a lower pH, higher glutathione and reactive oxygen species concentrations, and overexpression of some enzymes, facilitate the design of smart stimuli‐responsive gene carriers regulated by the tumor microenvironment. These carriers interact with nucleic acids and then form stable nanoparticles under physiological conditions. By regulation of the tumor microenvironment, stimuli‐responsive gene carriers are able to change their properties and achieve high gene delivery efficiency. Considering the tumor microenvironment as the “regulator” and “target” when designing gene carriers and choosing therapeutic genes shows significant benefit with respect to improving the accuracy and efficiency of cancer gene therapy.     

Integration of “Innate” and “Learned” Components within the IRME for Mussel Recognition in the European Bitterling Rhodeus amarus (Bloch)

The European bitterling (Rhodeus amarus Bloch) practises a rather unusual method of spawning by using the favorable conditions in the gills of a living freshwater mussel (genera Unio and Anodonta) for the embryonic development of its fry. The capacity of mussel recognition was studied in inexperienced individuals with the aid of simultaneous preference tests in which pairs of dummies with increasing similarity to mussels were presented to the animals. The frequency of mussel-referred motor patterns, which were supposed to be species-specific (Wiepkema 1961), supplied the evaluation criterion. The results revealed a hierarchy of effectiveness within the class of relevant stimuli and showed certain effects of additivity typical of an Innate Releasing Mechanism or IRM. By far the most effective stimulus consisted in the specific smell of the mussel which is composed of at least three constituents (protein, hyaluronic acid, ammonium). The water flow itself, produced by the mussel in order to maintain nutritive and respiratory functions, was effective depending on its velocity (3 < v < 12 cm/s), its orientation (suction produced no effect), its direction (vertical > horizontal) and the shape of its field (oval). Within the visual modality only two simple perceptory patterns could be detected (dark spot on a clearer surface, straight horizontal edge), but the visual shape of the mussel as a whole was ignored by inexperienced individuals. Nevertheless the bitterlings are able to learn the shape when exposed to a living mussel and, in addition, it was even possible to condition the animals to an artificial object (inverted pot of clay) by using the mussel-smell flow as a reinforcing stimulus. The final discussion deals with the question of whether it is possible to interpret these “innate” respectively “learned” components of the IRME as sensory counterparts of behavioral structures which simply serve different functions by referring to correspondingly different sectors of the environment. In such a case the epistemological dichotomy regularly associated with the notions of “innate” (= “pre-given phylogenetical knowledge”) and “learned” (= “cognitive increase during ontogeny”) would suffer incisive questioning.     

“Active” and “passive” ecological restoration strategies in meta‐analysis

One of the means of creating a more robust methodology for ecological restoration involves reducing the gap between ecological theory and restoration practices. A common strategy to do so is using meta‐analysis to understand key drivers of restoration outcomes. “Active” and “passive” is a dichotomy often used to separate restoration strategies in such meta‐analyses. We investigate previously raised concerns about selection bias and subjective categorization of strategies. We promote a paired experimental design in future empirical research and propose the use of three categories of restoration strategy in lieu of “passive” and “active” to alleviate inconsistency in definitions and categorization.     

Der „Sekundenkleber“ der Stummelfüßer

Novel insights into the “superglue” of velvet worms The biological “superglue” of velvet worms provides inspiration towards circular processing of advanced polymers. In nature, velvet worms employ a fluid, protein‐rich secretion for hunting and defense, which forms rapidly into stiff fibers. The fluid‐to‐fiber transition occurs outside the body without regulations, indicating that the “instructions” for assembly are programmed into the protein building blocks. Electrostatic interactions between oppositely charged protein domains and free ions drive protein folding, self‐organization (coacervation) and stabilization of the building blocks into nanoscale droplets. Yet, nanodroplets can be instantly transformed via simple mechanical stimulus as proteins partially unfold, merge together and form a strong network, which solidifies into a fiber. The mechanism is based on basic physico‐chemical principles. Thus, by extracting these principles, new methods of synthesizing sustainable polymer‐based materials can be developed.     

The “cratic correction” and related fallacies

The “cratic correction” for removing the contribution of translational motion from standard free energies and entropies of chemical reactions is examined. Although removal of translational effects is useful in interpreting free energy and entropy changes in molecular terms, this particular correction does not do so. No basis for it is found in thermodynamics or statistical mechanics. The appropriate correction for center-of-mass translational motion is derived from classical statistical mechanics. However, the importance of recognizing the proper molecular meaning of the remaining free energy is stressed. In any case, this latter correction, however legitimate, is shown to be futile, since it has long been recognized from classical statistical mechanics that all terms involving momenta (thermal wavelength terms) —be they classified as translational, rotational, vibrational, or whatever—necessarily cancel out informing the standard free energy change of any chemical reaction from the constituent standard chemical potentials. © 1995 John Wiley & Sons, Inc.     

THE ROLE OF PHYLLOTACTIC PATTERN AS A “DEVELOPMENTAL CONSTRAINT” ON THE INTERCEPTION OF LIGHT BY LEAF SURFACES

Computer simulations of model plants are used to assess the influence of leaf shape, size, and pattern of arrangement (= phyllotaxy) on the direct solar radiation intercepted by leaf surfaces. Changes in phyllotaxy significantly influence light interception (and, by inference, net assimilation rate) for rosette growth habits. However, changes in leaf shape and orientation and in stem length can compensate for the negative effects of leaf overlap produced by phyllotactic patterns. Phyllotaxy is viewed as a developmental limiting factor in photobiology that may necessitate compensatory changes in other morphological features not directly controlled by patterns of leaf initiation. This distinguishes it from functioning as a “developmental constraint” sensu stricto and may provide a paradigm for other features in plant evolution.     

Sneaker “jack” males outcompete dominant “hooknose” males under sperm competition in Chinook salmon (Oncorhynchus tshawytscha)

In a variety of taxa, males deploy alternative reproductive tactics to secure fertilizations. In many species, small “sneaker” males attempt to steal fertilizations while avoiding encounters with larger, more aggressive, dominant males. Sneaker males usually face a number of disadvantages, including reduced access to females and the higher likelihood that upon ejaculation, their sperm face competition from other males. Nevertheless, sneaker males represent an evolutionarily stable strategy under a wide range of conditions. Game theory suggests that sneaker males compensate for these disadvantages by investing disproportionately in spermatogenesis, by producing more sperm per unit body mass (the “fair raffle”) and/or by producing higher quality sperm (the “loaded raffle”). Here, we test these models by competing sperm from sneaker “jack” males against sperm from dominant “hooknose” males in Chinook salmon. Using two complementary approaches, we reject the fair raffle in favor of the loaded raffle and estimate that jack males were ~1.35 times as likely as hooknose males to fertilize eggs under controlled competitive conditions. Interestingly, the direction and magnitude of this skew in paternity shifted according to individual female egg donors, suggesting cryptic female choice could moderate the outcomes of sperm competition in this externally fertilizing species.     

“Capacity”, “best interests”, “will and preferences” and the UN Convention on the Rights of Persons with Disabilities

The United Nations (UN) Convention on the Rights of Persons with Disabilities (CRPD) is the most up‐to‐date international legal instrument concerning the rights of persons with disabilities. Such persons are taken to include those with serious mental disorders. According to an authoritative interpretation of a crucial Article (Article 12 ‐ Equal recognition before the law) by the UN CRPD Committee, involuntary detention and treatment of people with mental health disabilities are prohibited under the Convention. Both conventional mental health law and “capacity‐based” law are deemed to violate the Convention. However, some other UN bodies are not in full agreement (for example, the UN Human Rights Committee and the Subcommittee on Prevention of Torture and Other Cruel, Inhuman or Degrading Treatment or Punishment), while others are less explicitly absolutist (for example, the Human Rights Council). Furthermore, strong criticisms of the position of the CRPD Committee have been mounted from a number of academic quarters. These criticisms center on whether the role of a person's ability to make a decision can be ignored, no matter the circumstances. Much of the above debate turns on the concept of “legal capacity” and the now often‐repeated precept that one must always respect the “will and preferences” of the person with a disability. However, “will and preferences” remains undefined. In this paper, I offer an analysis of “will and preferences” that can clarify interventions that may be acceptable or non‐acceptable under the terms of the UN Convention.