Differential movement and movement bias models for marine protected areas

Marine protected areas (MPAs) are promoted as a tool to protect overfished stocks and increase fishery yields. Previous models suggested that adult mobility modified effects of MPAs by reducing densities of fish inside reserves, but increasing yields (i.e., increasing densities outside of MPAs). Empirical studies contradicted this prediction: as mobility increased, the relative density of fishes inside MPAs (relative to outside) increased or stayed constant. We hypothesized that this disparity between theoretical and empirical results was the result of differential movement of fish inside versus outside the MPA. We, therefore, developed a model with unequal and discontinuous diffusion, and analyzed its steady state and stability. We determined the abundance in the fishing grounds, the yield, the total abundance and the log ratio at steady-state and examined their response to adult mobility (while keeping the relative inequity in the diffusion constant). Abundance in the fishing grounds and yield increased, while total abundance and log-ratio decreased, as mobility increased. These results were all qualitatively consistent with the previous models assuming uniform diffusivity. Thus, the mismatch between empirical and theoretical results must result from other processes or other forms of differential movement. Therefore, we modified our original model by assuming that species located on the boundary of the MPA will preferentially move towards the MPA. This localized movement bias model gives rise to steady state profiles that can differ radically from the profiles in the unbiased model, especially when the bias is large. Moreover, for sufficiently large bias values, the monotonicity of the four measures with increased mobility is reversed, when compared with our original model. Thus, the movement bias model reconciles empirical data and theoretical results.     

Functional siRNAs and miRNAs exhibit strand bias

Both microRNAs (miRNA) and small interfering RNAs (siRNA) share a common set of cellular proteins (Dicer and the RNA-induced silencing complex [RISC]) to elicit RNA interference. In the following work, a statistical analysis of the internal stability of published miRNA sequences in the context of miRNA precursor hairpins revealed enhanced flexibility of miRNA precursors, especially at the 5'-anti-sense (AS) terminal base pair. The same trend was observed in siRNA, with functional duplexes displaying a lower internal stability (Delta0.5 kcal/mol) at the 5'-AS end than nonfunctional duplexes. Average internal stability of siRNA molecules retrieved from plant cells after introduction of long RNA sequences also shows this characteristic thermodynamic signature. Together, these results suggest that the thermodynamic properties of siRNA play a critical role in determining the molecule's function and longevity, possibly biasing the steps involved in duplex unwinding and strand retention by RISC.     

Primary rat sertoli and interstitial cells exhibit a differential response to cadmium

Two cell types central to the support of spermatogenesis, the Sertoli cell and the interstitial (Leydig) cell, were isolated from the same cohort of young male rats and challenged with cadmium chloride to compare their susceptibility to the metal. Both cell types were cultured under similar conditions, and similar biochemical endpoints were chosen to minimize experimental variability. These endpoints include the uptake of ¹⁰⁹Cd, reduction of the vital tetrazolium dye MTT, incorporation of ³ H-leucine, change in heat-stable cadmium binding capacity, and production of lactate. Using these parameters, it was observed that the Sertoli cell cultures were adversely affected in a dose-and time-dependent manner, while the interstitial cell cultures, treated with identical concentrations of CdCl₂, were less affected. The 72-hr LC₅₀'s for Sertoli cells and interstitial cells were 4.1 and 19.6 M CdCl₂, respectively. Thus, different cell populations within the same tissue may differ markedly in susceptibility to a toxicant. These in vitro data suggest that the Sertoli cell, in relation to the interstitium, is particularly sensitive to cadmium. Because the Sertoli cell provides functional support for the seminiferous epithelium, the differential sensitivity of this cell type may, in part, explain cadmium-induced testicular dysfunction, particularly at doses that leave the vascular epithelium intact.Abbreviations CBF cadmium-binding factor - DMEM Dulbecco's modified Eagle's medium - FSH follicle stimulating hormone - ICC interstitial cell culture - IGF-I insulin-like growth factor-I - LC(50) 50% lethal concentration - MTT 3-(4,5-dimethylthiazol-2-yl) - SCC Sertoli cell culture This work was supported by NIEHS ESO4141 and NIH HD-08358 (AHP).Preliminary results of some of this work were reported at the 26th Annual Meeting of the Society of Toxicology (1987), Washington, DC.     

Parallel visual motion processing streams for manipulable objects and human movements

We tested the hypothesis that different regions of lateral temporal cortex are specialized for processing different types of visual motion by studying the cortical responses to moving gratings and to humans and manipulable objects (tools and utensils) that were either stationary or moving with natural or artificially generated motions. Segregated responses to human and tool stimuli were observed in both ventral and lateral regions of posterior temporal cortex. Relative to ventral cortex, lateral temporal cortex showed a larger response for moving compared with static humans and tools. Superior temporal cortex preferred human motion, and middle temporal gyrus preferred tool motion. A greater response was observed in STS to articulated compared with unarticulated human motion. Specificity for different types of complex motion (in combination with visual form) may be an organizing principle in lateral temporal cortex.     

Reading faces: differential lateral gaze bias in processing canine and human facial expressions in dogs and 4-year-old children

Sensitivity to the emotions of others provides clear biological advantages. However, in the case of heterospecific relationships, such as that existing between dogs and humans, there are additional challenges since some elements of the expression of emotions are species-specific. Given that faces provide important visual cues for communicating emotional state in both humans and dogs, and that processing of emotions is subject to brain lateralisation, we investigated lateral gaze bias in adult dogs when presented with pictures of expressive human and dog faces. Our analysis revealed clear differences in laterality of eye movements in dogs towards conspecific faces according to the emotional valence of the expressions. Differences were also found towards human faces, but to a lesser extent. For comparative purpose, a similar experiment was also run with 4-year-old children and it was observed that they showed differential processing of facial expressions compared to dogs, suggesting a species-dependent engagement of the right or left hemisphere in processing emotions.     

Lefty proteins exhibit unique processing and activate the MAPK pathway

Lefty polypeptides, novel members of the transforming growth factor-beta (TGF-beta) superfamily, are involved in the formation of embryonic lateral patterning. Members of the TGF-beta superfamily require processing for their activation, suggesting cleavage to be an essential step for lefty activation. Transfection of different cell lines with lefty resulted in expression of a 42-kDa protein, which was proteolytically processed to release two polypeptides of 34 and 28 kDa. Since members of the proprotein convertase (PC) family cleave different TGF-beta factors and are involved in the establishment of embryonic laterality, we studied their role in lefty processing. Cotransfection analysis showed that PC5A processed the lefty precursor to the 34-kDa form in vivo, whereas furin, PACE4, PC5B, and PC7 had a limited activity. None of these PCs showed activity in the processing of the lefty polypeptide to the 28-kDa lefty form. The mutation of the consensus sequences for PC cleavage in the lefty protein allowed the lefty cleavage sites to be identified. Mutations of the sequence RGKR to GGKG (amino acids 74-77) and of RHGR to GHGR (amino acids 132-135) prevented the proteolytic processing of the lefty precursor to the 34- and 28-kDa forms, respectively. To identify the biologically active form of lefty, we studied the effect of lefty treatment on pluripotent P19 cells. Lefty did not induce Smad2 or Smad5 phosphorylation, Smad2/Smad4 heterodimerization, or nuclear translocation of Smad2 or Smad4, but activated the MAPK pathway in a time- and dose-dependent fashion. Further analysis showed the 28-kDa (but not the 34-kDa) polypeptide to induce MAPK activity. Surprisingly, the 42-kDa lefty protein was also capable of inducing MAPK activity, indicating that the lefty precursor is biologically active. The data support a molecular model of processing as a mechanism for regulation of lefty signaling.     

NK T cell precursors exhibit differential cytokine regulation and require Itk for efficient maturation

NK T cells are a lymphocyte lineage that is selected by CD1d and is characterized by the ability to rapidly secrete large amounts of both IFN-gamma and IL-4 after TCR stimulation. Using reactivity to CD1d tetramers to define presumptive NK T cells, several NK T cell progenitor populations were characterized based upon NK marker expression and CD4 vs CD8 expression. The earliest populations were found to be negative for NK markers and could proliferate to IL-7, while mature NK T cells did not. The NK1.1(-) NK T cell progenitors were capable of up-regulating NK1.1 when transferred in vivo. Upon stimulation, the NK1.1(-) populations secrete IL-4, but little IFN-gamma. As the cells mature and up-regulate NK1.1, they acquire the ability to secrete IFN-gamma. Finally, the Tec family tyrosine kinase Itk is necessary for optimal NK1.1 up-regulation and hence final maturation of NK T cells. The itk(-/-) mice also display a progressive decrease in NK T cells in older animals, suggesting a further role in peripheral maintenance.     

Polyadenylation proteins CstF-64 and tauCstF-64 exhibit differential binding affinities for RNA polymers

CstF-64 (cleavage stimulation factor-64), a major regulatory protein of polyadenylation, is absent during male meiosis. Therefore a paralogous variant, tauCstF-64 is expressed in male germ cells to maintain normal spermatogenesis. Based on sequence differences between tauCstF-64 and CstF-64, and on the high incidence of alternative polyadenylation in testes, we hypothesized that the RBDs (RNA-binding domains) of tauCstF-64 and CstF-64 have different affinities for RNA elements. We quantified K(d) values of CstF-64 and tauCstF-64 RBDs for various ribopolymers using an RNA cross-linking assay. The two RBDs had similar affinities for poly(G)18, poly(A)18 or poly(C)18, with affinity for poly(C)18 being the lowest. However, CstF-64 had a higher affinity for poly(U)18 than tauCstF-64, whereas it had a lower affinity for poly(GU)9. Changing Pro-41 to a serine residue in the CstF-64 RBD did not affect its affinity for poly(U)18, but changes in amino acids downstream of the C-terminal alpha-helical region decreased affinity towards poly(U)18. Thus we show that the two CstF-64 paralogues differ in their affinities for specific RNA sequences, and that the region C-terminal to the RBD is mportant in RNA sequence recognition. This supports the hypothesis that tauCstF-64 promotes germ-cell-specific patterns of polyadenylation by binding to different downstream sequence elements.     

Cyclosporin A and its non-immunosuppressive derivative exhibit a differential effect on cell-mediated mineralization in culture

Chronic immunosuppressive treatment with cyclosporin A (CsA) is associated with decreased bone density. However, in culture, CsA inhibits osteoclast differentiation and bone resorption. This raises the question as to whether CsA also affects osteoblast function. Immunophilin, one of the CsA-binding cyclophilins that is implicated in the immunosuppressive action of CsA via calcineurin, is a peptidyl prolyl cis-trans isomerase (PPI). CsA also binds a mitochondrial membrane PPI which is implicated in controlling permeability transition pores. Therefore, in the present study we tested the effect of CsA on cell mediated mineralization in parallel with mitochondrial rhodamine retention as an indicator of mitochondrial membrane potential. Rat marrow stromal cells were grown in dexamethasone (DEX) medium to stimulate mineralization in culture, and CsA was added to various cultures using different treatment schedules. Low dose (0.1 μM) CsA inhibited mineralization, compared to controls, when present in the cultures during days 3–11 of DEX stimulation. Contrarily, high dose CsA (1.0 μM) resisted the inhibitory effect of the low dose. SDZ 220–384 (SDZ), a non-immunosuppressive derivative of CsA which is known, like CsA, to bind to mitochondrial cyclophilin but does not inhibit calcineurin, was also tested. Both high and low doses of SDZ decreased mineralization when present in the cultures from day 3 or from day 0. The similar effect of the low CsA dose and SDZ on mineralization is in accord with their ability to block permeability transition pores. The differential effect, on day 21 mineralization, between high CsA dose and SDZ took place in parallel to their opposing effects on mitochondrial membrane potential. On days 4–8, mitochondrial rhodamine retention was higher under CsA than under SDZ. Under these conditions there was no significant difference between the effects of these drugs on cell proliferation measured on day 11; there was a minor decrease in specific alkaline phosphatase activity by SDZ, too small to explain the extent of mineralization inhibition by SDZ. These results suggest that permeability transition pores might be involved in controlling mineralization. Unlike SDZ, CsA exhibits an additional effect on the mitochondrial membrane potential and on mineralization when applied at a high dose on day 3. Therefore identifying the additional activity of high dose CsA, which is missing in SDZ, may be beneficial. Such activity is expected to resist changes in rhodamine retention and decreased mineralization induced by SDZ, and yet enable preservation of immunosuppressive activity of CsA. J. Cell. Biochem. 64:209–216. © 1997 Wiley-Liss, Inc.     

A differential geometry approach for biomedical image processing

We show in this paper how simple considerations about bio-arrays images lead to a peak segmentation allowing the genes activity analysis. Bio-arrays images have a particular structure and the aim of the paper is to present a mathematical method allowing their automatic processing. The differential geometry approach used here can be also employed for other types of images presenting grey level peaks corresponding to a functional activity or to a chemical concentration. The mathematical method is based on elementary techniques of differential geometry and dynamical systems theory and provides a simple efficient algorithm when the peaks to segment are isolated.     

GIGANTEA and EARLY FLOWERING 4 in Arabidopsis exhibit differential phase-specific genetic influences over a diurnal cycle

The endogenous circadian clock regulates many physiological processes related to plant survival and adaptability. GIGANTEA (GI), a clock-associated protein, contributes to the maintenance of circadian period length and amplitude, and also regulates flowering time and hypocotyl growth in response to day length. Similarly, EARLY FLOWERING 4 (ELF4), another clock regulator, also contributes to these processes. However, little is known about either the genetic or molecular interactions between GI and ELF4 in Arabidopsis. In this study, we investigated the genetic interactions between GI and ELF4 in the regulation of circadian clock-controlled outputs. Our mutant analysis shows that GI is epistatic to ELF4 in flowering time determination, while ELF4 is epistatic to GI in hypocotyl growth regulation. Moreover, GI and ELF4 have a synergistic or additive effect on endogenous clock regulation. Gene expression profiling of gi, elf4, and gi elf4 mutants further established that GI and ELF4 have differentially dominant influences on circadian physiological outputs at dusk and dawn, respectively. This phasing of GI and ELF4 influences provides a potential means to achieve diversity in the regulation of circadian physiological outputs, including flowering time and hypocotyl growth.     

Retinal cone and rod photoreceptor cells exhibit differential susceptibility to light-induced damage

All-trans-retinal and its condensation-products can cause retinal degeneration in a light-dependent manner and contribute to the pathogenesis of human macular diseases such as Stargardt's disease and age-related macular degeneration. Although these toxic retinoid by-products originate from rod and cone photoreceptor cells, the contribution of each cell type to light-induced retinal degeneration is unknown. In this study, the primary objective was to learn whether rods or cones are more susceptible to light-induced, all-trans-retinal-mediated damage. Previously, we reported that mice lacking enzymes that clear all-trans-retinal from the retina, ATP-binding cassette transporter 4 and retinol dehydrogenase 8, manifested light-induced retinal dystrophy. We first examined early-stage age-related macular degeneration patients and found retinal degenerative changes in rod-rich rather than cone-rich regions of the macula. We then evaluated transgenic mice with rod-only and cone-like-only retinas in addition to progenies of such mice inbred with Rdh8(-/-) Abca4(-/-) mice. Of all these strains, Rdh8(-/-) Abca4(-/-) mice with a mixed rod-cone population showed the most severe retinal degeneration under regular cyclic light conditions. Intense light exposure induced acute retinal damage in Rdh8(-/-) Abca4(-/-) and rod-only mice but not cone-like-only mice. These findings suggest that progression of retinal degeneration in Rdh8(-/-) Abca4(-/-) mice is affected by differential vulnerability of rods and cones to light.     

Bovine brain gray and white matter exhibit differential protein prenyl transferase activity

Protein farnesyl transferase and geranylgeranyl transferase-I activities were determined in gray and white matter from various regions of bovine brain. Farnesyl transferase activity was 3–8 times greater than geranylgeranyl transferase-I activity. However, farnesyl transferase activity was about 2 times greater in the white matter than in the gray matter in all regions of the brain. Mixing experiments indicated lack of farnesyl transferase activators in white matter. This difference in farnesyl transferase activity may be due to enzyme content and may have implications in brain cell function.     

Long-distance movement and differential targeting of microRNA399s

We have previously demonstrated that miR399s control phosphate (Pi) homeostasis by regulating the expression of a ubiquitin-conjugating E2 enzyme (UBC24/PHO2) in Arabidopsis. Changes in miR399-dependent PHO2 gene expression modulate Pi uptake, allocation and remobilization. More recently, we provided evidence that miR399s are able to move in the phloem stream and across grafting junctions from the scions overexpressing miR399 to the wild-type rootstocks. Movement of miR399s serves as a long-distance signal to report and balance the Pi status between shoots and roots. Of note, results from grafting experiments indicate that miR399b is less efficient in cleaving the PHO2 mRNA than is miR399f, despite the similar mobility of the two miR399s. We propose that nucleotide 13 of miR399s, which gives rise to the sequence variation among different miR399 species, could be involved in regulating the abundance of PHO2 mRNA through sequence complementarity to the target sequences of PHO2 mRNA and mimicking target sequence of At4/IPS1 noncoding RNAs.Key words: phosphate, microRNA399, PHO2, UBC24, long-distance movement, At4/IPS1     

Correcting the estimated level of differential expression for gene selection bias: application to a microarray study

The level of differential gene expression may be defined as a fold change, a frequency of upregulation, or some other measure of the degree or extent of a difference in expression across groups of interest. On the basis of expression data for hundreds or thousands of genes, inferring which genes are differentially expressed or ranking genes in order of priority introduces a bias in estimates of their differential expression levels. A previous correction of this feature selection bias suffers from a lack of generality in the method of ranking genes, from requiring many biological replicates, and from unnecessarily overcompensating for the bias. For any method of ranking genes on the basis of gene expression measured for as few as three biological replicates, a simple leave-one-out algorithm corrects, with less overcompensation, the bias in estimates of the level of differential gene expression. In a microarray data set, the bias correction reduces estimates of the probability of upregulation or downregulation from 100% to as low as 60%, even for genes with estimated local false discovery rates close to 0. A simulation study quantifies both the advantage of smoothing estimates of bias before correction and the degree of overcompensation.     

Optimizing the noise versus bias trade-off for Illumina whole genome expression BeadChips

Five strategies for pre-processing intensities from Illumina expression BeadChips are assessed from the point of view of precision and bias. The strategies include a popular variance stabilizing transformation and model-based background corrections that either use or ignore the control probes. Four calibration data sets are used to evaluate precision, bias and false discovery rate (FDR). The original algorithms are shown to have operating characteristics that are not easily comparable. Some tend to minimize noise while others minimize bias. Each original algorithm is shown to have an innate intensity offset, by which unlogged intensities are bounded away from zero, and the size of this offset determines its position on the noise-bias spectrum. By adding extra offsets, a continuum of related algorithms with different noise-bias trade-offs is generated, allowing direct comparison of the performance of the strategies on equivalent terms. Adding a positive offset is shown to decrease the FDR of each original algorithm. The potential of each strategy to generate an algorithm with an optimal noise-bias trade-off is explored by finding the offset that minimizes its FDR. The use of control probes as part of the background correction and normalization strategy is shown to achieve the lowest FDR for a given bias.     

European, Chinese and Japanese pear fruits exhibit differential softening characteristics during ripening

Softening characteristics were investigated in three types of pear fruit, namely, European pear 'La France', Chinese pear 'Yali', and Japanese pear 'Nijisseiki'. 'La France' fruit softened dramatically and developed a melting texture during ripening, while 'Yali' fruit with and without propylene treatment showed no change in flesh firmness and texture during ripening. Non-treated 'Nijisseiki' did not show a detectable decrease in flesh firmness, whereas continuous propylene treatment caused a gradual decrease in firmness resulting in a mealy texture. In 'La France', the analysis of cell wall polysaccharides revealed distinct solubilization and depolymerization of pectin and hemicellulose during fruit softening. In 'Nijisseiki', propylene treatment led to the solubilization and depolymerization of pectic polysaccharides to a limited extent, but not of hemicellulose. In 'Yali', hemicellulose polysaccharides were depolymerized during ripening, but there was hardly any change in pectic polysaccharides except in the water-soluble fraction. PC-PG1 and PC-PG2, two polygalacturonase (PG) genes, were expressed in 'La France' fruit during ripening, while only PC-PG2 was expressed in 'Nijisseiki' and neither PC-PG1 or PC-PG2 was expressed in 'Yali'. The expression pattern of PC-XET1 was constitutive during ripening in all three pear types. PG activity measured by the reducing sugar assay increased in all three pears during ripening. However, viscometric measurements showed that the levels of endo-PG activity were high in 'La France', low in 'Nijisseiki', and undetectable in 'Yali' fruits. These results suggest that, in pears, cell wall degradation is correlated with a decrease in firmness during ripening and the modification of both pectin and hemicellulose are essential for the development of a melting texture. Furthermore, the data suggest that different softening behaviours during ripening among the three pear fruits may be caused by different endo-PG activity and different expression of PG genes.