The “Balance of Nature”—Evolution of a Panchreston

The earliest concept of a balance of nature in Western thought saw it as being provided by gods but requiring human aid or encouragement for its maintenance. With the rise of Greek natural philosophy, emphasis shifted to traits gods endowed species with at the outset, rather than human actions, as key to maintaining the balance. The dominance of a constantly intervening God in the Middle Ages lessened interest in the inherent features of nature that would contribute to balance, but the Reformation led to renewed focus on such features, particularly traits of species that would maintain all of them but permit none to dominate nature. Darwin conceived of nature in balance, and his emphasis on competition and frequent tales of felicitous species interactions supported the idea of a balance of nature. But Darwin radically changed its underlying basis, from God to natural selection. Wallace was perhaps the first to challenge the very notion of a balance of nature as an undefined entity whose accuracy could not be tested. His skepticism was taken up again in the 20th century, culminating in a widespread rejection of the idea of a balance of nature by academic ecologists, who focus rather on a dynamic, often chaotic nature buffeted by constant disturbances. The balance-of-nature metaphor, however, lives on in large segments of the public, representing a fragile aspect of nature and biodiversity that it is our duty to protect.The notion of a “balance of nature” stretches back to early Greeks, who believed gods maintained it with the aid of human prayers, sacrifices, and rituals [1]. As Greek philosophers developed the idea of natural laws, human assistance in maintaining the balance did not disappear but was de-emphasized. Herodotus, for instance, the earliest known scholar to seek biological evidence for a balance of nature, asked how the different animal species each maintained their numbers, even though some species ate other species. Amassing facts and factoids, he saw divinely created predators'' reproductive rates lower than those of prey, buttressing the idea of a providentially determined balance with a tale of a mutualism between Nile crocodiles beset with leeches and a plover species that feeds on them [1]. Two myths in Plato''s Dialogues supported the idea of a balance of nature: the Timaeus myth, in which different elements of the universe, including living entities, are parts of a highly integrated “superorganism,” and the Protagoras myth, in which gods created each animal species with characteristics that would allow it to thrive and, having run out of biological traits, had to give man fire and superior intelligence [1]. Among Romans, Cicero followed Herodotus and Plato in advancing a balance of nature generated by different reproductive rates and traits among species, as well as interactions among species [1].The Middle Ages saw less interest in such pre-set devices as differential reproductive rates to keep nature in balance, perhaps because people believed in a God who would maintain the balance by frequent direct intervention [1]. The Reformation, however, fostered further development of the concept of a providential balance of nature set in motion at creation. Thomas Browne [2] added differential mortality rates to factors maintaining the balance, and Matthew Hale [3] proposed that lower rates of mortality for humans than for other animals maintain human dominance within a balanced nature and added vicissitudes of heat from the sun to the factors keeping any one species from getting out of hand.The discovery of fossils that could not be ascribed to known living species severely challenged the idea of a God-given balance of nature, as they contradicted the idea of species divinely created with the necessary features for survival [4]. John Ray [5] suggested that the living representatives of such fossils would be found in unexplored parts of the earth, a solution that was viable until the great scientific explorations of the late 18th and early 19th centuries [4]. Ray also argued that what would now be termed different Grinnellian ecological niches demonstrated God''s provision of each species with a space of its own in nature.According to Egerton [1], the earliest use of the term “balance” to refer specifically to ecology was probably by Ray''s disciple, William Derham [6], who asserted in 1714 that:

“The Balance of the Animal World is, throughout all Ages, kept even, and by a curious Harmony and just Proportion between the increase of all Animals, and the length of their Lives, the World is through all Ages well, but not over-stored.”

Derham recognized that human populations seemed to be endlessly increasing but saw this fact as a provision by God for future disasters. This explanation contrasts with that of Linnaeus [7], who saw human and other populations endlessly increasing but believed the size of the earth was also increasing to accommodate them. Derham grappled with the issue of theodicy but failed to reconcile plagues of noxious animals with the balance of nature, seeing them rather as “Rods and Scourges to chastise us, as means to excite our Wisdom, Care, and Industry” [1].Derham''s contemporary Richard Bradley [8],[9] focused more on biological facts and less on Providence in sketching a more comprehensive account of an ecological balance of nature, taking account of the rapidly expanding knowledge of biodiversity, noting that each plant had its phytophagous insects, each insect its parasitic wasps or flies and predatory birds, concluding that “all Bodies have some Dependence upon one another; and that every distinct Part of Nature''s Works is necessary for the Support of the rest; and that if any one was wanting, all the rest must consequently be out of Order.” Thus, he saw the balance as fragile rather than robust, in spite of a constantly intervening God. Linnaeus [10] similarly marshaled observations of species interactions to explain why no species increases to crowd out all others, adding competition to the predation, parasitism, and herbivory adduced by Bradley and also emphasizing the different roles (we might now say “niches”) of different species as allowing them all to coexist in a sort of superorganismic, balanced whole.Unlike Derham, Georges-Louis Leclerc, Comte de Buffon [11] managed to reconcile animal plagues with a balanced nature. He perceived the balance of nature as dynamic, with all species fluctuating between relative rarity and abundance, so that whenever a species became overabundant, weather, predation, and competition for food would bring it back into balance. Buffon''s successor as director of the Jardin des Plantes in Paris, Jacques-Henri Bernardin de Saint-Pierre [12], was probably the first to associate ecological damage caused by biological invasions with a disruption of the balance of nature. Observing damage to introduced trees from insects accidentally introduced with them, he argued that failure to introduce the birds that would eat the insects led to the damage. William Paley [13], perhaps the inspiration for today''s advocates of “intelligent design,” analogized nature to a watch. One would assume a smoothly running watch was designed with purpose, and so too nature was designed by God with balance and a purpose.In the 19th century, evolution burst on the scene, greatly influencing and ultimately modifying conceptions of a balance of nature. Fossils that seemed unrelated to any living species, as noted above, conflicted with the balance of nature, because they implied extinction, a manifestly unbalanced event that furthermore could be seen to imply that God had made a mistake. Whereas Ray had been able to argue that living exemplars of fossil species would be found in unexplored parts of the earth, by the 19th century, this explanation could be rejected. Jean-Baptiste Lamarck [14] resolved the conflict in a different way, arguing that species continually change, so the balance remains the same. The fossils thus represent ancestors of living species, not extinct lineages. Robert Chambers [15], another early evolutionist, similarly saw fossils not as a paradox in a balanced nature but as a consequence of the fact that, as the physical environment changed, species either evolved or went extinct.Alfred Russel Wallace was perhaps the first to question the very existence of a balance of nature, in a remarkable notebook entry, ca. 1855:

“Some species exclude all others in particular tracts. Where is the balance? When the locust devastates vast regions and causes the death of animals and man, what is the meaning of saying the balance is preserved… To human apprehension there is no balance but a struggle in which one often exterminates another” [16].

In modern parlance, Wallace appears almost to be asking how “balance” could be defined in such a way that a balance of nature could be a testable hypothesis.Darwin''s theory of evolution by natural selection certainly explained the existence of fossils, and his emphasis on inevitable competition both between and within species downplayed the role of niche specialization propounded by Plato, Cicero, Linnaeus, Derham, and others [1]. Darwin nevertheless saw the ecological roles of the diversity of species as parts of an almost superorganismic nature, and his main contribution to the idea of a balance of nature was his constant emphasis on competition and other mortality factors that kept all species'' populations in check [1]. His many metaphors and examples of the interactions among species, such as the tangled bank and the spinsters-cats-mice-bumblebees-clover stories in The Origin of Species [17], contributed to a sense of a highly balanced nature, but one driven by natural selection constantly changing species, rather than by God either intervening or creating species with traits that ensure their continued existence. Unlike Wallace, Darwin did not raise the issue of whether nature was actually balanced and how we would know if it was not.As ecology developed in the late 19th and early 20th centuries, it was inevitable that Wallace''s question—how to define “balance”—would be raised again and that increasingly wide and quantitative study, especially at the population level, would be brought to bear on the matter. The work of the early dominant plant ecologist Frederic Clements and his followers, with Clements'' notion of superorganismic communities [18], provided at least tacit support for the idea of a balance of nature, but his contemporary Charles Elton [19], a founder of the field of animal ecology and a leading student of animal population cycles, forcefully reprised Wallace''s concern:

“‘The balance of nature’ does not exist, and perhaps never has existed. The numbers of wild animals are constantly varying to a greater or lesser extent, and the variations are usually irregular in period and always irregular in amplitude. Each variation in the numbers of one species causes direct and indirect repercussions on the numbers of the others, and since many of the latter are themselves independently varying in numbers, the resultant confusion is remarkable.”

Despite Elton''s explicit skepticism, his depiction of energy flow through food chains and food webs was incorporated as a superorganismic analog to the physiology of individuals (e.g., [20]). Henry Gleason, another critic of the superorganism concept, who depicted populations distributed independently, rather than in highly organized communities, was ignored at this time [21].However, beginning with three papers in Ecological Monographs in 1947, the superorganism concept was increasingly questioned and, within 25 years, Gleason was vindicated and his views largely accepted by ecologists [22]. During this same period, extensive work by population biologists again took up Elton''s focus on population trajectories and contributed greatly to a growing recognition of the dynamism of nature and the fact that much of this dynamism did not seem regular or balanced [21]. The idea of a balanced nature did not immediately disappear among ecologists. For instance, a noteworthy book by C. B. Williams [23], Patterns in the Balance of Nature, described the distribution of abundances within communities or regions as evincing statistical regularity that might be construed as a type of “balance of nature,” at least if changes in individual populations do not change certain statistical features (a hypothesis that Williams considered untested at the time). But the predominant view by ecologists of the 1960s saw the whole notion of a balance as, at best, irrelevant and, at worst, a distraction. Ehrlich and Birch [24], for example, ridiculed the idea:

“The existence of supposed balance of nature is usually argued somewhat as follows. Species X has been in existence for thousands or perhaps millions of generations, and yet its numbers have never increased to infinity or decreased to zero. The same is true of the millions of other species still extant. During the next 100 years, the numbers of all these species will fluctuate; yet none will increase indefinitely, and only a few will become extinct… Such ‘observations’ are made the basis for the statement that population size is ‘controlled’ or ‘regulated,’ and that drastic changes in size are the results of upsetting the ‘balance of nature.’”

Another line of ecological research that became popular at the end of the 20th century was to equate “balance of nature” with some sort of equilibrium of numbers, usually of population sizes [25], but sometimes of species richness. The problem remained that, with numbers that vary for whatever reason, it is still arbitrary just how much temporal variation can be accommodated within a process or phenomenon for it still to be termed equilibrial [26]. Often the decision on whether to perceive an ecological process as equilibrial seems to be based on whether there is some sort of homeostatic regulation of the numbers, such as density-dependence, which A. J. Nicholson [27] suggested as an argument against Elton''s skepticism of the existence of a balance. The classic 1949 ecology text by Allee et al. [28] explicitly equated balance with equilibrium and cited various mechanisms, such as density-dependence, in support of its universality in nature [25]. Later similar sorts of mathematical arguments equated the mathematical stability of models representing nature with a balance of nature [29], although the increasing recognition of stochastic aspects and chaotic mathematics of population fluctuations made it more difficult to perceive a balanced nature in population trajectories [21].For academic ecologists, the notion of a balance of nature has become passé, and the term is widely recognized as a panchreston [30]—a term that means so many different things to different people that it is useless as a theoretical framework or explanatory device. Much recent research has been devoted to emphasizing the dynamic aspects of nature and prominence of natural or anthropogenic disturbances, particularly as evidenced by vicissitudes of population sizes, and advances the idea that there is no such thing as a long-term equilibrium (e.g., [31],[32]). Some authors explicitly relate this research to a rejection of the concept of a balance of nature (e.g., [33]–[35]), Pickett et al. [33] going so far as to say it must be replaced by a different metaphor, the “flux of nature.”The issue is confounded by the fact that the perception of balance can be sought at different levels (populations, communities, ecosystems) and spatial scales. Much of the earlier discussion of a balance was at the population and community levels—Browne, Hale, Bradley, Linnaeus, Buffon, Bernardin de Saint-Pierre, and Darwin saw balance in the limited fluctuations of populations and the interactions of populations as one force imposing the limits. The proponents of density-dependent population regulation fall in this category as well [36],[37]. As a balance is sought at the community and ecosystem levels, the sorts of evidence brought to bear on the matter become more complicated and abstract [37],[38]. It is increasingly difficult to imagine what sorts of empirical or observational data could test the notion of a balance. For instance, Williams''s balance of nature—evidenced by a particular statistical distribution of population sizes—would not be perceived as balanced by many observers in light of the fact that entire populations can crash, explode, or even go extinct within the constraint of a statistical distribution of a given shape. Early claims of a balance at the highest level, such as the various superorganisms (Plato''s Timaeus myth, Paley''s watch metaphor, Clements''s superorganismic plant community) can hardly be seen as anything other than metaphors rather than testable hypotheses and have fallen from favor. The most expansive conception of a balance of nature—the Gaia hypothesis [39]—has been almost universally rejected by scientists [40]. The advent and growing acceptance of the metapopulation concept of nature [41] also complicates the search for balance in bounded population fluctuations. Spatially limited individual populations can arise, fluctuate wildly, and even go extinct, while suitable dynamics maintain the widespread metapopulation as a whole.Yet, the idea of a balance of nature lives on in the popular imagination, especially among conservationists and environmentalists. However, the usual use of the metaphor in an environmental context suggests that the balance, whether given by God or produced by evolution, is a fragile balance, one that needs human actions for its maintenance. Through the 18th century, the balance of nature was probably primarily a comforting construct—it would protect us; it represented some sort of benign governance in the face of occasional awful events. When Darwin replaced God as the determinant of the balance with natural selection, the comfort of a balance of nature was not so overarching, if there was any comfort at all. Today, ecologists do not even recognize a balance, and those members of the public who do, see it as something we must protect if we are ever to reap benefits from it in the future (e.g., wetlands that might help ameliorate flooding from storms and sea-level rise). This shift is clear in the writings of Bill McKibben [42],[43], who talks frequently about balance, but about balance with nature, not balance of nature, and how humankind is headed towards a catastrophic future if it does not act promptly and radically to rebalance society with nature.     

Evolution of the Pretoria Saltpan — a diatom record spanning a full glacial-interglacial cycle

Hydrobiologia - In 1988–89 a 200 m core was drilled down to granite bedrock in the Pretoria Saltpan as part of a project to ascertain the origin of this unusual feature. The top 90 m of the...     

The heart—a different approach

The study of bryophytes forms an obvious part of school, college, and university courses which deal with cytology and developmental behaviour. They are readily obtained, conveniently cultured, and require fewer specialized skills than are necessary for similar work on other organisms. Information on preparing mitotic chromosomes for examination is provided, as are details of a technique by which Giemsa C-banding of chromosomes becomes for the first time a realistic proposition at all levels of education. Practical firsthand experience of the latter technique provides a useful way of coordinating the teaching of microscopic and molecular aspects of cell biology. Cytological behaviour can also be related to experiments on developmental aspects of the life cycle, a cycle which is noted for its well-marked alternation of generations. These include suggestions for monitoring the seasonal maturation of gametangia and sporophytes, as well as for examining photolropic responses made in liverworts by diploid setae and haploid archegoniophores.     

Evolution of a Vκ gene family

To examine the evolution of multigene families we have selected as an example an immunoglobulin light chain variable region subgroup (V24) which has been extensively characterized in inbred mice (Mus musculus domesticus). Homologous genes have been isolated and sequenced from Mus pahari, a genetically and geographically isolated species believed to be the oldest living representative of the genus. Southern blot analysis using probes corresponding to individual genes in this subgroup reveals changes in the overall size of the family occurring at the level of individual genes but not at the level of the entire family. Nucleotide sequence analysis indicates an absence of regulatory sequences such as the CAT and TATA boxes 5 to the coding region, but a decanucleotide sequence involved in light chain expression is highly conserved. Within coding regions highly complex patterns of variation are seen which appear to reflect quite different selective pressures on various subregions of the coding sequence. Complementarity determining regions (CDR) are conserved to different extents, with the first CDR region in all family members being among the most conserved segments of the molecule. Conservation is similarly variable among framework segments, indicating complex and variable evolutionary pressures not only at the level of individual genes or their products but also at subregions within homologous molecules.     

Bioremediation of multi-metal contaminated soil using biosurfactant — a novel approach

An unconventional nutrient medium, distillery spent wash (1:3) diluted) was used to produce di-rhamnolipid biosurfactant by Pseudomonas aeruginosa strain BS2. This research further assessed the potential of the biosurfactant as a washing agent for metal removal from multimetal contaminated soil (Cr-940 ppm; Pb-900 ppm; Cd-430 ppm; Ni-880 ppm; Cu-480 ppm). Out of the treatments of contaminated soil with tap water and rhamnolipid biosurfactant, the latter was found to be potent in mobilization of metal and decontamination of contaminated soil. Within 36 hours of leaching study, di-rhamnolipid as compared to tap water facilitated 13 folds higher removal of Cr from the heavy metal spiked soil whereas removal of Pb and Cu was 9–10 and 14 folds higher respectively. Leaching of Cd and Ni was 25 folds higher from the spiked soil. This shows that leaching behavior of biosurfactant was different for different metals. The use of wastewater for production of biosurfactant and its efficient use in metal removal make it a strong applicant for bioremediation.     

Identification of chilling and heat requirements of cherry trees—a statistical approach

Most trees from temperate climates require the accumulation of winter chill and subsequent heat during their dormant phase to resume growth and initiate flowering in the following spring. Global warming could reduce chill and hence hamper the cultivation of high-chill species such as cherries. Yet determining chilling and heat requirements requires large-scale controlled-forcing experiments, and estimates are thus often unavailable. Where long-term phenology datasets exist, partial least squares (PLS) regression can be used as an alternative, to determine climatic requirements statistically. Bloom dates of cherry cv. ‘Schneiders späte Knorpelkirsche’ trees in Klein-Altendorf, Germany, from 24 growing seasons were correlated with 11-day running means of daily mean temperature. Based on the output of the PLS regression, five candidate chilling periods ranging in length from 17 to 102 days, and one forcing phase of 66 days were delineated. Among three common chill models used to quantify chill, the Dynamic Model showed the lowest variation in chill, indicating that it may be more accurate than the Utah and Chilling Hours Models. Based on the longest candidate chilling phase with the earliest starting date, cv. ‘Schneiders späte Knorpelkirsche’ cherries at Bonn exhibited a chilling requirement of 68.6?±?5.7 chill portions (or 1,375?±?178 chilling hours or 1,410?±?238 Utah chill units) and a heat requirement of 3,473?±?1,236 growing degree hours. Closer investigation of the distinct chilling phases detected by PLS regression could contribute to our understanding of dormancy processes and thus help fruit and nut growers identify suitable tree cultivars for a future in which static climatic conditions can no longer be assumed. All procedures used in this study were bundled in an R package (‘chillR’) and are provided as Supplementary materials. The procedure was also applied to leaf emergence dates of walnut (cv. ‘Payne’) at Davis, California.     

Characterization of polychlorinated alkane mixtures—a Monte Carlo modeling approach

A Monte Carlo model was developed to characterize the molecular composition of polychlorinated alkane mixtures. The model is based upon a simulation of the free-radical chlorination process by which polychlorinated alkane mixtures are produced industrially from n-alkanes. In the model, the free-radical chlorination reaction was simulated by randomly selecting a position on a partially converted alkane molecule for target by chlorine free-radical attack. The relative reactivities of the hydrogen atoms on the alkane chain towards chlorine free-radical substitution were either determined experimentally or extrapolated from experimental results and incorporated into the model. The result of the simulation is the prediction of the detailed molecular composition of any PCA mixture. Good agreement was found when comparing the distribution of molecules predicted by the model to analytically determined distributions of real PCA mixtures. Results from the model were then coupled with rules describing the action of biological enzymes to estimate the upper limit possible for the aerobic biodegradation of PCA mixtures.     

Evolution Observed—Some Examples of Evolution Occurring in Historical Times

In an earlier article it was suggested that the 13 species of Darwin finch flew to the Galapagos islands, and did not spéciale in the archipelago. Following criticism of this idea, the theory is presented in more detail, the criticisms are answered, and the original educational role of the theory is reaffirmed.     

Prodrugs for masking bitter taste of antibacterial drugs—a computational approach

DFT calculations for the acid-catalyzed hydrolysis of several maleamic acid amide derivatives revealed that the reaction rate-limiting step is determined on the nature of the amine leaving group. Further, it was established that when the amine leaving group was a secondary amine, acyclovir or cefuroxime moiety the tetrahedral intermediate formation was the rate-limiting step such as in the cases of acyclovir ProD 1- ProD 4 and cefuroxime ProD 1- ProD 4. In addition, the linear correlation between the calculated and experimental rates provided a credible basis for designing prodrugs for masking bitter taste of the corresponding parental drugs which have the potential to release the parent drug in a sustained release fashion. For example, based on the DFT calculated rates the predicted t_1/2 (a time needed for 50 % of the reactant to be hydrolyzed to products) for cefuroxime prodrugs, cefuroxime ProD 1- ProD 4, were 12 min, 18 min, 200 min and 123 min, respectively.

LCA in architectural design—a parametric approach

Purpose

Life cycle assessment (LCA) has not been widely applied in the building design process because it is perceived to be complex and time-consuming. There is a high demand for simplified approaches that architects can use without detailed knowledge of LCA. This paper presents a parametric LCA approach, which allows architects to efficiently reduce the environmental impact of building designs.

Methods

First, the requirements for design-integrated LCA are analyzed. Then, assumptions to simplify the required data input are made and a parametric model is established. The model parametrizes all input, including building geometry, materials, and boundary conditions, and calculates the LCA in real time. The parametric approach possesses the advantage that input parameters can be adjusted easily and quickly. The architect has two options to improve the design: either through manually changing geometry, building materials, and building services, or through the use of an optimization solver. The parametric model was implemented in a parametric design software and applied using two cases: (a) the design of a new multi-residential building, and (b) retrofitting of a single-family house.

Results and discussion

We have successfully demonstrated the capability of the approach to find a solution with minimum environmental impact for both examples. In the first example, the parametric method is used to manually compare geometric design variants. The LCA is calculated based on assumptions for materials and building services. In the second example, evolutionary algorithms are employed to find the optimum combination of insulation material, heating system, and windows for retrofitting. We find that there is not one optimum insulation thickness, but many optima, depending on the individual boundary conditions and the chosen environmental indicator.

Conclusions

By incorporating a simplified LCA into the design process, the additional effort of performing LCA is minimized. The parametric approach allows the architect to focus on his main task of designing the building and finally makes LCA practically useful for design optimization. In the future, further performance analysis capabilities such as life cycle costing can also be integrated.

     

Centres of diversity quantified—A maximum variance approach to a biogeographic problem

Summary A quantitative method that optimizes the mapping of species diversity in phytogeographic studies is described. Diversity is computed on the basis of species number per unit area. The optimal size of unit area for which diversity is computed is held to be that which maximises the diversity difference between species-rich and species-poor regions. An example is given using Turkish Papaver. A very high correspondence is found between intuitive insights based on long study and the computer-generated diversity maps. Phytogeographic elements were also determined by computer after gridding Turkey at the scale discovered to be optimal for diversity and scoring the grid squares for presence-absence of each species. In this case, too, quite high correspondence was found between the computer and intuitive results.Nomenclature follows Cullen (1965).The authors express their thanks to Mr. K. Roberts, University of Western Ontario Computing Centre of writing the original maximum variance program and to the National Research Council of Canada for supporting the computing side of the project.     

Nutrient retention function of a stream wetland complex—A high-frequency monitoring approach

The ability of riverine ecosystems to retain nutrients depends on different hydrological, chemical and biological conditions including exchange processes between streams and wetlands. We investigated nutrient retention in a stream wetland complex on the time scale of daily hydrological exchange between both systems. Daily mass balances of NO₃-N, NH₄-N, TP and SRP were calculated with data obtained by two automated measurement stations in a stream reach upstream and downstream of a wetland. The pattern of hydrological exchange between stream and wetland was used to classify characteristic hydrological periods like floods, base and low flows. The nutrient retention function of the stream wetland complex varied considerably during phases of similar hydrologic conditions. Despite re-wetting measures in the wetland, an overall net export of all nutrients except for NH₄-N characterised the whole growing season. Nitrate retention occurred during summer flood (retention in the wetland, 23 kg NO₃-N d^?1, 17% of the input load) and low flow (retention in the stream, 1 kg NO₃-N d^?1, 2% of the input load). TP retention during summer could be assigned to sedimentation (0.7 kg TP d^?1, 7% during flooding in the wetland, 0.2 kg TP d^?1, 4% during low flow in the stream). SRP retention was only intermittent. We concluded that the nutrient retention of streams and wetlands can only be optimised by restoration measures that regard both systems as one functional unit in terms of nutrient retention.     

Prodrugs of fumarate esters for the treatment of psoriasis and multiple sclerosis—a computational approach

Density functional theory (DFT) calculations at B3LYP/6-31 G (d,p) and B3LYP/6-311?+?G(d,p) levels for the substituted pyridine-catalyzed isomerization of monomethyl maleate revealed that isomerization proceeds via four steps, with the rate-limiting step being proton transfer from the substituted pyridinium ion to the C=C double bond in INT1. In addition, it was found that the isomerization rate (maleate to fumarate) is solvent dependent. Polar solvents, such as water, tend to accelerate the isomerization rate, whereas apolar solvents, such as chloroform, act to slow down the reaction. A linear correlation was obtained between the isomerization activation energy and the dielectric constant of the solvent. Furthermore, linearity was achieved when the activation energy was plotted against the pK _a value of the catalyst. Substituted-pyridine derivatives with high pK _a values were able to catalyze isomerization more efficiently than those with low pK _a values. The calculated relative rates for prodrugs 1–6 were: 1 (406.7), 2 (7.6?×?10⁶), 3 (1.0), 4 (20.7), 5 (13.5) and 6 (2.2?×?10³). This result indicates that isomerizations of prodrugs 1 and 3–5 are expected to be slow and that of prodrugs 2 and 6 are expected to be relatively fast. Hence, prodrugs 2 and 3–5 have the potential to be utilized as prodrugs for the slow release of monomethylfumarate in the treatment of psoriasis and multiple sclerosis.

Early Evolution of the Vertebrate Eye—Fossil Evidence

Evidence of detailed brain morphology is illustrated and described for 400-million-year-old fossil skulls and braincases of early vertebrates (placoderm fishes). Their significance is summarized in the context of the historical development of knowledge of vertebrate anatomy, both before and since the time of Charles Darwin. These ancient extinct fishes show a unique type of preservation of the cartilaginous braincase and demonstrate a combination of characters unknown in other vertebrate species, living or extinct. The structure of the oldest detailed fossil evidence for the vertebrate eye and brain indicates a legacy from an ancestral segmented animal, in which the braincase is still partly subdivided, and the arrangement of nerves and muscles controlling eye movement was intermediate between the living jawless and jawed vertebrate groups. With their unique structure, these placoderms fill a gap in vertebrate morphology and also in the vertebrate fossil record. Like many other vertebrate fossils elucidated since Darwin’s time, they are key examples of the transitional forms that he predicted, showing combinations of characters that have never been observed together in living species.     

Temporal relationships of a pulse of prolactin (PRL) to a pulse of a metabolite of PGF2α in mares

Hourly blood samples were collected from 10 mares during 24 h of each of the preluteolytic, luteolytic, and postluteolytic periods. The autocorrelation function of the R program was used to detect pulse rhythmicity, and the intra-assay CV was used to locate and characterize pulses of prolactin (PRL) and a metabolite of prostaglandin F2α (PGFM). Rhythmicity of PRL and PGFM concentrations was detected in 67% and 89% of mares, respectively. Combined for the three periods (no difference among periods), the PRL pulses were 5.2 ± 0.4 h (mean ± SEM) at the base, 7.5 ± 1.5 h between nadirs of adjacent pulses, and 12.3 ± 1.5 h from peak to peak. The peaks of PRL pulses were greater (P < 0.05) during the luteolytic period (46 ± 14 ng/mL) and postluteolytic period (52 ± 15 ng/mL) than during the preluteolytic period (17 ± 3 ng/mL). Concentrations of PRL during hours of a PGFM pulse were different (P < 0.003) within the luteolytic period and postluteolytic period and were greatest at the PGFM peak; PRL concentrations during a PGFM pulse were not different during the preluteolytic period. The frequency of the peak of PRL and PGFM pulses occurring at the same hour (synchrony) was greater for the luteolytic period (65%, P < 0.01) and postluteolytic period (50%, P < 0.001) than for the preluteolytic period (17%). This is the first report in mares on characterization and rhythmicity of PRL pulses, synchrony between PRL and PGFM pulses, and greater PRL activity during the luteolytic and postluteolytic periods than during the preluteolytic period.