Notes

Increasing antitumor defense employing antiangiogenic brokers: Mechanistic information, existing development, and specialized medical challenges.
Widely observed allometric scaling (log-log slope less then 1) of metabolic rate (MR) with body mass (BM) in animals has been frequently explained using functional mechanisms, but rarely studied from the perspective of multivariate quantitative genetics. This is unfortunate, given that the additive genetic slope (bA) of the MR-BM relationship represents the orientation of the 'line of least genetic resistance' along which MR and BM may most likely evolve. Here, we calculated bA in eight species. Although most bA values were within the range of metabolic scaling exponents reported in the literature, uncertainty of each bA estimate was large (only one bA was significantly lower than 3/4 and none were significantly different from 2/3). Overall, the weighted average for bA (0.667±0.098 95% CI) is consistent with the frequent observation that metabolic scaling exponents are negatively allometric in animals (b less then 1). Although bA was significantly positively correlated with the phenotypic scaling exponent (bP) across the sampled species, bP was usually lower than bA, as reflected in a (non-significantly) lower weighted average for bP (0.596±0.100). This apparent discrepancy between bA and bP resulted from relatively shallow MR-BM scaling of the residuals [weighted average residual scaling exponent (be)=0.503±0.128], suggesting regression dilution (owing to measurement error and within-individual variance) causing a downward bias in bP. Our study shows how the quantification of the genetic scaling exponent informs us about potential constraints on the correlated evolution of MR and BM, and by doing so has the potential to bridge the gap between micro- and macro-evolutionary studies of scaling allometry.The magnitude of many kinds of biological traits relates strongly to body size. Therefore, a first step in comparative studies frequently involves correcting for effects of body size on the variation of a phenotypic trait, so that the effects of other biological and ecological factors can be clearly distinguished. However, commonly used traditional methods for making these body-size adjustments ignore or do not completely separate the causal interactive effects of body size and other factors on trait variation. Various intrinsic and extrinsic factors may affect not only the variation of a trait, but also its covariation with body size, thus making it difficult to remove completely the effect of body size in comparative studies. These complications are illustrated by several examples of how body size interacts with diverse developmental, physiological, behavioral and ecological factors to affect variation in metabolic rate both within and across species. Such causal interactions are revealed by significant effects of these factors on the body-mass scaling slope of metabolic rate. I discuss five possible major kinds of methods for removing body-size effects that attempt to overcome these complications, at least in part, but I hope that my Review will encourage the development of other, hopefully better methods for doing so.Speed regulation in animals involves stride frequency and stride length. While the relationship between these variables has been well documented, it remains unresolved whether animals primarily modify stride frequency or stride length to increase speed. In this study, we explored the interrelationships between these three variables across a sample of 103 tetrapods and assessed whether speed regulation strategy is influenced by mechanical, allometric, phylogenetic or ecological factors. We observed that crouched terrestrial species tend to regulate speed through stride frequency. Such a strategy is energetically costly, but results in greater locomotor maneuverability and greater stability. In contrast, regulating speed through stride length is closely tied to larger arboreal animals with relatively extended limbs. Such movements reduce substrate oscillations on thin arboreal supports and/or helps to reduce swing phase costs. The slope of speed on frequency is lower in small crouched animals than in large-bodied erect species. As a result, substantially more rapid limb movements are matched with only small speed increases in crouched, small-bodied animals. Furthermore, the slope of speed on stride length was inversely proportional to body mass. As such, small changes in stride length can result in relatively rapid speed increases for small-bodied species. These results are somewhat counterintuitive, in that larger species, which have longer limbs and take longer strides, do not appear to gain as much speed increase out of lengthening their stride. Conversely, smaller species that cycle their limbs rapidly do not gain as much speed out of increasing stride frequency as do larger species.There is growing interest in studying hormones beyond single 'snapshot' measurements, as recognition that individual variation in the endocrine response to environmental change may underlie many rapid, coordinated phenotypic changes. Repeated measures of hormone levels in individuals provide additional insight into individual variation in endocrine flexibility - that is, how individuals modulate hormone levels in response to the environment. The ability to quickly and appropriately modify phenotype is predicted to be favored by selection, especially in unpredictable environments. The need for repeated samples from individuals can make empirical studies of endocrine flexibility logistically challenging, but methods based in mathematical modeling can provide insights that circumvent these challenges. NSC663284 Our Review introduces and defines endocrine flexibility, reviews existing studies, makes suggestions for future empirical work, and recommends mathematical modeling approaches to complement empirical work and significantly advance our understanding. Mathematical modeling is not yet widely employed in endocrinology, but can be used to identify innovative areas for future research and generate novel predictions for empirical testing.Field crickets (Family Gryllidae, Subfamily Gryllinae) typically produce tonal calls with carrier frequencies in the range 3-8 kHz. In this study, we explored the use of a finite element model (FEM) of the stridulatory apparatus of a field cricket, Gryllus bimaculatus, based on experimental measurements of resonator geometry and mechanical properties, to predict the measured call carrier frequencies of eight other field cricket species, ranging between 3 and 7 kHz. The model allowed accurate predictions of carrier frequencies for all eight species to within a few hundred hertz from morphological measurements of their resonators. We then used the model to explore the plausible evolutionary design space for field cricket call carrier frequency along the axes of resonator size and thickness, and mapped the locations of the nine experimentally measured species in this design space. Although the nine species spanned the evolutionarily conserved spectrum of carrier frequency and body size in field crickets, they were clustered in a small region of the available design space. We then explored the reasons for this apparent evolutionary constraint on field cricket carrier frequencies at both the lower and higher limit. We found that body size and sound radiation efficiency were the main constraints at the lower limits, whereas the energetics of stridulation using the clockwork mechanism may pose a constraint at higher frequencies.The difficulty of quantifying asymmetrical limb movements, compared with symmetrical gaits, has resulted in a dearth of information concerning the mechanics and adaptive benefits of these locomotor patterns. Further, no study has explored the evolutionary history of asymmetrical gaits using phylogenetic comparative techniques. Most foundational work suggests that symmetrical gaits are an ancestral feature and asymmetrical gaits are a more derived feature of mammals, some crocodilians, some turtles, anurans and some fish species. In this study, we searched the literature for evidence of the use of asymmetrical gaits across extant gnathostomes, and from this sample (n=308 species) modeled the evolution of asymmetrical gaits assuming four different scenarios. Our analysis shows strongest support for an evolutionary model where asymmetrical gaits are ancestral for gnathostomes during benthic walking and could be both lost and gained during subsequent gnathostome evolution. We were unable to reconstruct the presence/absence of asymmetrical gaits at the tetrapod, amniote, turtle and crocodilian nodes with certainty. The ability to adopt asymmetrical gaits was likely ancestral for Mammalia but was probably not ancestral for Amphibia and Lepidosauria. The absence of asymmetrical gaits in certain lineages may be attributable to neuromuscular and/or anatomical constraints and/or generally slow movement not associated with these gaits. This finding adds to the growing body of work showing the early gnathostomes and tetrapods may have used a diversity of gaits, including asymmetrical patterns of limb cycling.Suction feeding in ray-finned fishes requires substantial muscle power for fast and forceful prey capture. The axial musculature located immediately behind the head has been long known to contribute some power for suction feeding, but recent XROMM and fluoromicrometry studies found nearly all the axial musculature (over 80%) provides effectively all (90-99%) of the power for high-performance suction feeding. The dominance of axial power suggests a new framework for studying the musculoskeletal biomechanics of fishes the form and function of axial muscles and bones should be analysed for power production in feeding (or at least as a compromise between swimming and feeding), and cranial muscles and bones should be analysed for their role in transmitting axial power and coordinating buccal expansion. This new framework is already yielding novel insights, as demonstrated in four species for which suction power has now been measured. Interspecific comparisons suggest high suction power can be achieved in different ways increasing the magnitude of suction pressure or the rate of buccal volume change, or both (as observed in the most powerful of these species). Our framework suggests that mechanical and evolutionary interactions between the head and the body, and between the swimming and feeding roles of axial structures, may be fruitful areas for continued study.Comparative analyses have a long history of macro-ecological and -evolutionary approaches to understand structure, function, mechanism and constraint. As the pace of science accelerates, there is ever-increasing access to diverse types of data and open access databases that are enabling and inspiring new research. Whether conducting a species-level trait-based analysis or a formal meta-analysis of study effect sizes, comparative approaches share a common reliance on reliable, carefully curated databases. Unlike many scientific endeavors, building a database is a process that many researchers undertake infrequently and in which we are not formally trained. This Commentary provides an introduction to building databases for comparative analyses and highlights challenges and solutions that the authors of this Commentary have faced in their own experiences. We focus on four major tips (1) carefully strategizing the literature search; (2) structuring databases for multiple use; (3) establishing version control within (and beyond) your study; and (4) the importance of making databases accessible.
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