A continued role for signaling functions in the early evolution of feathers

Persons and Currie (2015) argued against either flight, thermoregulation, or signaling as a functional benefit driving the earliest evolution of feathers; rather, they favored simple feathers having an initial tactile sensory function, which changed to a thermoregulatory function as density increased. Here, we explore the relative merits of early simple feathers that may have originated as tactile sensors progressing instead toward a signaling, rather than (or in addition to) a thermoregulatory function. We suggest that signaling could act in concert with a sensory function more naturally than could thermoregulation. As such, the dismissal of a possible signaling function and the presumption that an initial sensory function led directly to a thermoregulatory function (implicit in the title “bristles before down”) are premature.     

AMP-activated protein kinase (AMPK) regulates autophagy,inflammation and immunity and contributes to osteoclast differentiation and functionabs

Osteoclasts are multinucleated giant cells, responsible for bone resorption. Osteoclast differentiation and function requires a series of cytokines to remove the old bone, which coordinates with the induction of bone remodelling by osteoblast-mediated bone formation. Studies have demonstrated that AMP-activated protein kinase (AMPK) play a negative regulatory role in osteoclast differentiation and function. Research involving AMPK, a nutrient and energy sensor, has primarily focused on osteoclast differentiation and function; thus, its role in autophagy, inflammation and immunity remains poorly understood. Autophagy is a conservative homoeostatic mechanism of eukaryotic cells, and response to osteoclast differentiation and function; however, how it interacts with inflammation remains unclear. Additionally, based on the regulatory function of different AMPK subunits for osteoclast differentiation and function, its activation is regulated by upstream factors to perform bone metabolism. This review summarises the critical role of AMPK-mediated autophagy, inflammation and immunity by upstream and downstream signalling during receptor activator of nuclear factor kappa-B ligand-induced osteoclast differentiation and function. This pathway may provide therapeutic targets for bone-related diseases, as well as function as a biomarker for bone homoeostasis.     

The NF2 tumor suppressor Merlin and the ERM proteins interact with N-WASP and regulate its actin polymerization function

The function of the NF2 tumor suppressor merlin has remained elusive despite increasing evidence for its role in actin cytoskeleton reorganization. The closely related ERM proteins (ezrin, radixin, and moesin) act as linkers between the cell membrane and cytoskeleton, and have also been implicated as active actin reorganizers. We report here that merlin and the ERMs can interact with and regulate N-WASP, a critical regulator of actin dynamics. Merlin and moesin were found to inhibit N-WASP-mediated actin assembly in vitro, a function that appears independent of their ability to bind actin. Furthermore, exogenous expression of a constitutively active ERM inhibits N-WASP-dependent Shigella tail formation, suggesting that the ERMs may function as inhibitors of N-WASP function in vivo. This novel function of merlin and the ERMs illustrates a mechanism by which these proteins directly exert their effects on actin reorganization and also provides new insight into N-WASP regulation.     

Human Ovarian Function and Reproductive Ecology: New Hypotheses

A series of eight hypotheses is presented, based on the results of current research, concerning the responsiveness of the human ovary to constitutional and environmental variables. These hypotheses are motivated by a theoretical position that seeks to understand human reproductive physiology as the product of natural selection. The hypotheses are: (1) Ovarian responsiveness occurs along a graded continuum. (2) The graded continuum of response forms a final common pathway for various "stresses." (3) Ovarian function tracks energy balance, not simply nutritional status. (4) Ovarian function tracks aerobic activity independently of energy balance. (5) Additive interactions characterize the interaction of constitutional and environmental factors modulating ovarian function. (6) Reproductive maturation is synchronized with skeletal maturation, especially of the pelvis. (7) Peak ovarian function is not ordinarily achieved until the early twenties. (8) Late reproductive maturation is associated with a slower rise in indices of ovarian function with age, and a lower level of ovarian function in adulthood. Together, these hypotheses provide for two, non-exclusive theories of facultative modulation of female reproductive effort. One theory views ovarian function as responsive to the prospects for positive reproductive outcome as these may be affected by maternal age, maturation, energy balance, and activity level. The second theory views ovarian function as responsive in a similar way to the need to maintain long-term maternal energy balance.     

KIDNEY FUNCTION TESTS IN CHILDREN

Total renal function is best determined by urinalysis and serum creatinine determination. This may be supplemented, under controlled conditions, by fractional urinary phenosulfonphthalein clearance. The excretory urogram, while invaluable as a diagnostic test, lacks quantitative value as a function test.Until recently, individual renal function determinations depended upon the difficult and tedious cystoscopy and bilateral ureteral catheterization and skilled laboratory techniques. Frequently the necessity of anesthesia artificially depressed kidney function.Since 1956, the radioisotope kidney function test has offered an external, innocuous means of assessing individual renal blood flow, function and drainage plus evaluation of vesico-ureteral reflux. The method has distinct advantages for evaluation of pediatric urological problems.     

Connectance in Sorghum development: beyond the genotype-phenotype duality

A new approach to syntax and semantics of language is presented as a form of function dynamics, which is studied both analytically and numerically. The iteration of the function dynamics leads to articulation and formation of rules, which depend on each other. A hierarchy of meta-rules as rules of rules also emerges through the iteration when the initial function is suitably embedded. Iteration of a model with dialogue between two function dynamics is shown to generate a higher level structure.     

Acetoacetate Accelerates Muscle Regeneration and Ameliorates Muscular Dystrophy in Mice

Acetoacetate (AA) is a ketone body and acts as a fuel to supply energy for cellular activity of various tissues. Here, we uncovered a novel function of AA in promoting muscle cell proliferation. Notably, the functional role of AA in regulating muscle cell function is further evidenced by its capability to accelerate muscle regeneration in normal mice, and it ameliorates muscular dystrophy in mdx mice. Mechanistically, our data from multiparameter analyses consistently support the notion that AA plays a non-metabolic role in regulating muscle cell function. Finally, we show that AA exerts its function through activation of the MEK1-ERK1/2-cyclin D1 pathway, revealing a novel mechanism in which AA serves as a signaling metabolite in mediating muscle cell function. Our findings highlight the profound functions of a small metabolite as signaling molecule in mammalian cells.     

Four notions of biological function

I argue that there are at least four different ways in which the term ‘function’ is used in connection with the study of living organisms, namely: (1) function as (mere) activity, (2) function as biological role, (3) function as biological advantage, and (4) function as selected effect. Notion (1) refers to what an item does by itself; (2) refers to the contribution of an item or activity to a complex activity or capacity of an organism; (3) refers to the value for the organism of an item having a certain character rather than another; (4) refers to the way in which a trait acquired and has maintained its current share in the population. The recognition of a separate notion of function as biological advantage solves the problem of the indeterminate reference situation that has been raised against a counterfactual analysis of function, and emphasizes the importance of counterfactual comparison in the explanatory practice of organismal biology. This reveals a neglected problem in the philosophy of biology, namely that of accounting for the insights provided by counterfactual comparison.     

Principles underlying mammalian neocortical scaling

 The neocortex undergoes a complex transformation from mouse to whale. Whereas synapse density remains the same, neuron density decreases as a function of gray matter volume to the power of around −1/3, total convoluted surface area increases as a function of gray matter volume to the power of around 8/9, and white matter volume disproportionately increases as a function of gray matter volume to the power of around 4/3. These phylogenetic scaling relationships (including others such as neuron number, neocortex thickness, soma radius, and number of cortical areas) are clues to understanding the principles driving neocortex organization, but there is currently no theory that can explain why these neocortical quantities scale as they do. Here I present a two-part model that explains these neocortical allometric scaling laws. The first part of the model is a special case of the physico-mathematical model recently put forward to explain the quarter power scaling laws in biology. It states that the neocortex is a space-filling neural network through which materials are efficiently transported, and that synapse sizes do not vary as a function of gray matter volume. The second part of the model states that the neocortex is economically organized into functionally specialized areas whose extent of area-interconnectedness does not vary as a function of gray matter volume. The model predicts, among other things, that the number of areas and the soma radius increase as a function of gray matter volume to the power of 1/3 and 1/9, respectively, and empirical support is demonstrated for each. Also, the scaling relationships imply that, although the percentage of the total number of neurons to which a neuron connects falls as a function of gray matter volume with exponent −1/3, the network diameter of the neocortex is invariant at around two. Finally, I discuss how a similar approach may have promise in explaining the scaling relationships for the brain and other organs as a function of body mass. Received: 23 December 1999 / Accepted in revised form: 2 August 2000     

Possible link between converting enzyme inhibition and renomedullary interstitial cells

The kidney exerts both prohypertensive and antihypertensive functions. Part of the anti-hypertensive function of the kidney is mediated by the renomedullary interstitial cells (RIC), as an endocrine-type function. Six experimental models of hypertension and their relation to the antihypertensive function of the RIC are discussed. It is proposed that the anti-hypertensive function of the RIC may be deficient by the three mechanisms: 1) absence of the cells (as in the renoprival state); 2) severe damage to the cells (as in partial nephrectomy-salt hypertension of the rat and late malignant hypertension of the rabbit); and 3) constraint of the function of these cells (as in angiotensin-salt hypertension due to a lower salt intake). The constraint may result from excessive angiotensin, either by a direct effect or via a hemodynamic mechanism. The converting enzyme inhibitors (CEI) fail to exert their antihypertensive function when the RIC are absent or damaged. Conversely, the CEI are effective in those models associated with intact RIC. CEI appear to exert their antihypertensive action partly through an effect on RIC.     

Experimental tests of sex allocation theory with two species of simultaneously hermaphroditic acorn barnacles

Sex allocation theory for simultaneous hermaphrodites predicts increases in relative allocation to male-specific function as competition for fertilizations increases. Theoretical models developed specifically for competing acorn barnacles predict that the proportional allocation to male function increases toward an asymptote of 50% as the number of competitors for fertilizations increases. Experimental manipulations were used to investigate how mate competition affected both relative and absolute allocation to the sex functions for two species of acorn barnacle: Semibalanus balanoides and Balanus glandula. The ratio of male to female allocation did not increase with the number of competitors for either species. However, both species showed increased allocation to male function (estimated as total mass of sex-specific tissues) with increased crowding. Allocation to female function seemed to be limited by other factors and did not vary with mating group size as predicted. Allocation to male and female function were both positively related to body size, but a trade-off between male and female function, a key assumption of prior models, was not observed.     

Small molecule approach to studying protein tyrosine phosphatase

Understanding the function of protein tyrosine phosphatases (PTPs) is crucial to deciphering cellular signaling in higher organisms. Of the 100 putative PTPs in human genome, only a little is known about their precise biological functions. Thus establishing novel ways to study PTP function remains a top priority among researchers. Classical genetics and more recently the use of RNA interference (RNAi) for gene silencing remains a popular choice to study function. However, the one gene-one function hypothesis is now recognized as an oversimplified scenario, especially among the signaling proteins such as PTPs. Therefore, there is a need to understand gene function in an appropriate cellular context. Since proteins are the work horses of the cell, alteration of protein function by various means is a particularly attractive strategy. In this context, the chemical approach, where a small molecule is used to affect the function of the desired protein is increasingly being recognized as a method of choice. In this review, we describe how small molecules can be used to study the function of a prototypical PTP, PTP1B, which is a negative regulator in insulin signaling. This includes our initial strategies for finding the most potent and specific PTP1B inhibitor to date, synthesizing cell permeable analogues suitable for cellular studies, and using them to dissect the role of PTP1B in the insulin signaling pathway. This approach is potentially general and thus could be utilized to study the function of other PTPs.     

Amplitude,frequency and phase determinants of perceived rotations and rigidity in the kinetic depth effect

In a previous experiment the author has shown how perceived rotations, in the kinetic depth effect, decrease as a function of temporal frequency. It was argued that many of the ambiguous motion effects, and the temporally limited nature of the phenomenon, are due to the inability to discriminate curvature and torsion information as well as the finite time required to extract these latter sequentially dependent image parameters. In this paper we extend the investigation to consider the perception of rotations and rigidity as a function of complexity, including amplitude and phase differences between image elements. Results indicate that perceived rigidity is specifically a function of phase information, or relative motion components, and that rotations decrease as a function of complexity. In this way the curvature and torsion extraction processes are integrated with the sinusoidal nature of the image motion.     

A generalized information function applied to the genetic code

The problem of the partitioning of the degeneracy of the codons in the genetic code is considered in the framework of a generalized information function IG = c sigma kpk(ln pk + G(Ek] where k represents the number of codons in a specific degeneracy class and G(Ek) is an arbitrary real valued function. For G(Ek) = 0 the Shannon information function is recovered. For a particular choice of G(Ek) that takes the dominance of even degeneracies into account, it is found by direct numerical calculations that the correct degeneracy partitioning appears as optimal values of the Ig function. This results is also supported by optimization calculations in which the generalized information function is regarded as a continuous function in the degeneracy variables.     

Sperm competition and the evolution of ejaculate composition

We present a model of sperm competition that incorporates both sperm and nonsperm parts of the ejaculate. Our primary focus is on determining how ejaculate composition and size evolves as a function of the effects of seminal fluid on male reproductive success and as a function of asymmetry in sperm usage by females. The model predicts that different patterns of investment in sperm and seminal products are expected to evolve as a function of the bias in sperm usage by females. It also predicts the evolution of distinct patterns in ejaculate composition depending on the function of seminal fluid. In the discussion, we highlight a number of potential approaches for testing the theory that we develop.     

Changes in prostacyclin and thromboxane biosynthesis and their catabolic enzyme activity in kidneys of aging rats

The effects of aging on the prostacyclin and thromboxane biosynthesis and prostaglandin catabolic enzyme activity in rat kidney were investigated. The prostacyclin biosynthesis, using arachidonic acid as substrate, was the greatest in young kidneys (2 months old) and then progressively decreased in mature (12 months old) and old (24 months old) kidneys, while thromboxane biosynthetic activity showed no significant change as a function of age. When prostaglandin H2 was used as substrate, the prostacyclin and thromboxane biosynthesis showed similar results as when arachidonic acid was used as substrate; the prostacyclin biosynthesis progressively decreased and thromboxane biosynthesis showed no significant change as a function of age. The fatty acid cyclooxygenase in kidney was measured by a specific radioimmunoassay. No significant change in renal fatty acid cyclooxygenase as a function of age was found. Thus, we concluded that the progressive decrease in renal prostacyclin biosynthesis as a function of age is due to a defect in prostacyclin synthetase in aged kidneys. The prostaglandin catabolic enzyme, NAD+-dependent 15-hydroxyprostaglandin dehydrogenase, in kidneys was also investigated. The enzyme activity progressively decreased as a function of age, which suggested a decrease in the metabolism of thromboxane A2 in aged kidneys. The present results, indicating a decrease in renal prostacyclin biosynthesis and renal 15-hydroxyprostaglandin dehydrogenase activity with aging, might contribute to a plausible explanation of the progressive decrease in renal functions in the elderly.     

Zipf's law in importance of genes for cancer classification using microarray data

Using a measure of how differentially expressed a gene is in two biochemically/phenotypically different conditions, we can rank all genes in a microarray dataset. We have shown that the falling-off of this measure (normalized maximum likelihood in a classification model such as logistic regression) as a function of the rank is typically a power-law function. This power-law function in other similar ranked plots are known as the Zipf's law, observed in many natural and social phenomena. The presence of this power-law function prevents an intrinsic cutoff point between the "important" genes and "irrelevant" genes. We have shown that similar power-law functions are also present in permuted dataset, and provide an explanation from the well-known chi(2) distribution of likelihood ratios. We discuss the implication of this Zipf's law on gene selection in a microarray data analysis, as well as other characterizations of the ranked likelihood plots such as the rate of fall-off of the likelihood.