bluuebunny/crossref_metadata_2025 huggingface dataset:
Light-emitting filaments composed of nanometer-sized carbon hollow capsules
Authors: Asaka Koji , Kato Ryoei , Maezono Yoshinari , Yoshizaki Ryozo , Miyazawa Kun’ichi , Kizuka Tokushi
Published: February 2006

Filaments composed of multilayered carbon hollow capsules less than 10nm in diameter have been synthesized from crystalline whiskers of fullerene C60 of submicrometer in diameter by preliminary heating at 1373K and successive impression of current. The structural, electrical and optical properties of the filaments were studied by in situ transmission electron microscopy combined with the functions of scanning probe microscopy. We found that the filaments easily emit visible light at a maximum wavelength of 700-730 nm by the application of a few volts.
Lewy bodies
Authors: Shults Clifford W.
Published: February 2006

Lewy bodies (LB) in the substantia nigra are a cardinal pathological feature of Parkinson's disease, but they occur in a number of neurodegenerative diseases and can be widespread in the nervous system. The characteristics, locations, and composition of LB are reviewed, with particular attention to α-synuclein (α-SYN), which appears to be the major component of LB. The propensity for α-SYN, a presynaptic protein widely expressed in the brain, to aggregate is because of an amyloidogenic central region. The factors that favor the aggregation of α-SYN and mechanisms of toxicity are examined, and a mechanism through which aggregates of α-SYN could induce mitochondrial dysfunction and/or release of proapoptotic molecules is proposed.
Presenilin-1 uses phospholipase D1 as a negative regulator of β-amyloid formation
Authors: Cai Dongming , Netzer William J. , Zhong Minghao , Lin Yixin , Du Guangwei , Frohman Michael , Foster David A. , Sisodia Sangram S. , Xu Huaxi , Gorelick Fred S. , Greengard Paul
Published: February 2006

Presenilin (PS1/PS2) is a major component of γ-secretase, the activity that mediates proteolysis of β-amyloid precursor protein to generate β-amyloid (Aβ). Here we demonstrate that PS1, through its loop region, binds to phospholipase D1 (PLD1), thereby recruiting it to the Golgi/trans-Golgi network. Overexpression of wild-type PLD1 reduces Aβ generation. Conversely, down-regulation of endogenous PLD1 by small hairpin RNA elevates Aβ production. The Aβ-lowering effect of PLD1 is independent of its ability to promote vesicular budding of β-amyloid precursor protein. The data indicate that overexpression of PLD1 decreases, and down-regulation of PLD1 increases, the catalytic activity, and the association of the subunits, of γ-secretase.
Phospholipase D1 corrects impaired βAPP trafficking and neurite outgrowth in familial Alzheimer’s disease-linked presenilin-1 mutant neurons
Authors: Cai Dongming , Zhong Minghao , Wang Runsheng , Netzer William J. , Shields Dennis , Zheng Hui , Sisodia Sangram S. , Foster David A. , Gorelick Fred S. , Xu Huaxi , Greengard Paul
Published: February 2006

Presenilins (PS1/PS2) regulate proteolysis of β-amyloid precursor protein (βAPP) and affect its intracellular trafficking. Here, we demonstrate that a PS1-interacting protein, phospholipase D1 (PLD1), affects intracellular trafficking of βAPP. Overexpression of PLD1 in PS1wt cells promotes generation of βAPP-containing vesicles from the trans-Golgi network. Conversely, inhibition of PLD1 activity by 1-butanol decreases βAPP trafficking in both wt and PS1-deficient cells. The subcellular localization of PLD1 is altered, and PLD enzymatic activity is reduced in cells expressing familial Alzheimer’s disease (FAD) PS1 mutations compared with PS1wt cells. Overexpression of wt, but not catalytically inactive, PLD1 increases budding of βAPP-containing vesicles from the trans-Golgi network in FAD mutant cells. Surface delivery of βAPP is also increased by PLD1 in these cells. The impaired neurite outgrowth capacity in FAD mutant neurons was corrected by introducing PLD1 into these cells. The results indicate that PLD1 may represent a therapeutic target for rescuing compromised neuronal function in AD.
Overview of the National Centralized Tokamak programme
Authors: Kikuchi M. , Tamai H. , Matsukawa M. , Fujita T. , Takase Y. , Sakurai S. , Kizu K. , Tsuchiya K. , Kurita G. , Morioka A. , Hayashi N. , Miura Y. , Itoh S. , Bialek J. , Navratil G. , Ikeda Y. , Fujii T. , Kurihara K. , Kubo H. , Kamada Y. , Miya N. , Suzuki T. , Hamamatsu K. , Kawashima H. , Kudo Y. , Masaki K. , Takahashi H. , Takechi M. , Akiba M. , Okuno K. , Ishida S. , Ichimura M. , Imai T. , Hashizume  , Miura Y. M. , Horiike H. , Kimura A. , Tsutsui H. , Matsuoka M. , Uesugi Y. , Sagara A. , Nishimura A. , Shimizu A. , Sakamoto M. , Nakamura K. , Sato K. , Okano K. , Ida K. , Shimada H.R. , Kishimoto Y. , Azechi H. , Tanaka S. , Yatsu K. , Yoshida N. , Inutake M. , Fujiwara M. , Inoue N. , Hosogane N. , Kuriyama M. , Ninomiya H.
Published: February 2006

An overview is given of the National Centralized Tokamak (NCT) programme as a research programme for advanced tokamak research to succeed JT-60U. The mission of NCT is to establish high beta steady-state operation for DEMO and to contribute to ITER. The machine flexibility is pursued in aspect ratio and shape controllability for the demonstration of the high-β steady-state, feedback control of resistive wall modes, wide current and pressure profile control capability and also very long pulse steady-state operation. Existing JT-60 infrastructure such as the heating and current drive system, power supplies and cooling systems will be best utilized for this modification.
Pregnancy weight gain: marmoset and tamarin dads show it too
Authors: Ziegler Toni E , Prudom Shelley L , Schultz-Darken Nancy J , Kurian Aimee V , Snowdon Charles T
Published: February 2006

Paternal behaviour is critical for the survival of offspring in many monogamous species. Common marmoset (
Callithrix jacchus)
and cotton-top tamarin (
Saguinus oedipus
) fathers spend as much or more time caring for infants than mothers. Expectant males of both species showed significant increases in weight across the pregnancy whereas control males did not (five consecutive months for marmoset males and six months for cotton-top tamarin males). Expectant fathers might be preparing for the energetic cost of fatherhood by gaining weight during their mate's pregnancy.
Lamb wave propagation in elastic waveguides with variable thickness
Authors: Pagneux Vincent , Maurel Agnès
Published: February 2006

The problem of Lamb wave propagation in waveguides with varying height is treated by a multimodal approach. The technique is based on a rearrangement of the equations of elasticity that provides a new system of coupled mode equations preserving energy conservation. These coupled mode equations avoid the usual problem at the cut-offs with zero wavenumber. Thereafter, we define an impedance matrix that is governed by a Riccati equation yielding a stable numerical computation of the solution. Incidentally, the versatility of the multimodal method is exemplified by treating analytically the case of slowly varying guide and by showing how to get easily the Green tensor in any geometry. The method is applied for a waveguide whose height is described by a Gaussian function and the energy conservation in verified numerically. We determine the Green tensor in this geometry.
Conformally Osserman four-dimensional manifolds whose conformal Jacobi operators have complex eigenvalues
Authors: Brozos-Vázquez M , García-Río E , Vázquez-Lorenzo R
Published: February 2006

Conformal Osserman four-dimensional manifolds are studied with special attention to the construction of new examples showing that the algebraic structure of any such curvature tensor can be realized at the differentiable level. As a consequence one gets examples of anti-self-dual manifolds whose anti-self-dual curvature operator has complex eigenvalues.
The method of fundamental solutions for eigenproblems in domains with and without interior holes
Authors: Tsai C.C , Young D.L , Chen C.W , Fan C.M
Published: February 2006

The main purpose of the present paper is to provide a general method of fundamental solution (MFS) formulation for two- and three-dimensional eigenproblems without spurious eigenvalues. The spurious eigenvalues are avoided by utilizing the mixed potential method. Illustrated problems in the annular and concentric domains are studied analytically and numerically to demonstrate the issue of spurious eigenvalues by the discrete and continuous versions of the MFS with and without the mixed potential method. The proposed numerical method is then verified with the exact solutions of the benchmark problems in circular and spherical domains with and without holes. Further studies are performed in a three-dimensional peanut shaped domain. In the spirit of the MFS, this scheme is free from meshes, singularities and numerical integrations.
Cortisol levels are positively associated with pup-feeding rates in male meerkats
Authors: Carlson Anne A , Manser Marta B , Young Andrew J , Russell Andrew F , Jordan Neil R , McNeilly Alan S , Clutton-Brock Tim
Published: February 2006

In societies of cooperative vertebrates, individual differences in contributions to offspring care are commonly substantial. Recent attempts to explain the causes of this variation have focused on correlations between contributions to care and the protein hormone prolactin, or the steroid hormone testosterone. However, such studies have seldom considered the importance of other hormones or controlled for non-hormonal factors that are correlative with both individual hormone levels and contributions to care. Using multivariate statistics, we show that hormone levels explain significant variation in contributions to pup-feeding by male meerkats, even after controlling for non-hormonal effects. However, long-term contributions to pup provisioning were significantly and positively correlated with plasma levels of cortisol rather than prolactin, while plasma levels of testosterone were not related to individual patterns of pup-feeding. Furthermore, a playback experiment that used pup begging calls to increase the feeding rates of male helpers gave rise to parallel increases in plasma cortisol levels, whilst prolactin and testosterone levels remained unchanged. Our findings confirm that hormones can explain significant amounts of variation in contributions to offspring feeding, and that cortisol, not prolactin, is the hormone most strongly associated with pup-feeding in cooperative male meerkats.
Ecological and genetic impact of Atlantic cod larval drift in the Skagerrak
Authors: Stenseth Nils Chr , Jorde Per Erik , Chan Kung-Sik , Hansen Elizabeth , Knutsen Halvor , André Carl , Skogen Morten D , Lekve Kyrre
Published: February 2006

We evaluate the hypothesis that Atlantic cod larvae are passively transported by sea currents from off-shore spawning areas to settle in coastal waters, a hypothesis which has recently gained support from genetic analysis of cod in the North Sea–Skagerrak area. Such larval transport has been suggested to be an important mechanism behind the commonly observed low spatial genetic differentiation in many marine organisms. Here, we apply an ARMAX(2,2) model for juvenile abundance and use long-term monitoring data from the Skagerrak coast, constituting 54 continuous annual series from 1945 to 1997. Analysing the model, we find that the product of the size of the North Sea breeding stock and the strength of the net inflow of North Sea waters had a significant, positive effect on the abundance of coastal juvenile cod. The peak effect occurs during the month of March, just after spawning, when eggs and larvae remain pelagic and sensitive to currents. In contrast, we find no evidence of any direct effect of the North Sea spawning stock alone. Our analyses indicate that 15–20 000 0-group larvae from the North Sea reach each fjord per year, on average. This corresponds to about 1–10% of the total 0-group population in each fjord on average. These findings clearly demonstrate a direct link between larval drift and gene flow in the marine environment.
Prevalence and evolutionary relationships of haematozoan parasites in native versus introduced populations of common mynaAcridotheres tristis
Authors: Ishtiaq Farah , Beadell Jon S , Baker Allan J , Rahmani Asad R , Jhala Yadvendradev V , Fleischer Robert C
Published: February 2006

The success of introduced species is frequently explained by their escape from natural enemies in the introduced region. We tested the enemy release hypothesis with respect to two well studied blood parasite genera (PlasmodiumandHaemoproteus) in native and six introduced populations of the common mynaAcridotheres tristis. Not all comparisons of introduced populations to the native population were consistent with expectations of the enemy release hypothesis. Native populations show greater overall parasite prevalence than introduced populations, but the lower prevalence in introduced populations is driven by low prevalence in two populations on oceanic islands (Fiji and Hawaii). When these are excluded, prevalence does not differ significantly. We found a similar number of parasite lineages in native populations compared to all introduced populations. Although there is some evidence that common mynas may have carried parasite lineages from native to introduced locations, and also that introduced populations may have become infected with novel parasite lineages, it may be difficult to differentiate between parasites that are native and introduced, because malarial parasite lineages often do not show regional or host specificity.
Complex
Mhc
-based mate choice in a wild passerine
Authors: Bonneaud Camille , Chastel Olivier , Federici Pierre , Westerdahl Helena , Sorci Gabriele
Published: February 2006

The extreme polymorphism of the vertebrate major histocompatibility complex (
Mhc
) is famous for protecting hosts against constantly evolving pathogens. Mate choice is often evoked as a means of maintaining
Mhc
variability through avoidance of partners with similar
Mhc
alleles or preference for heterozygotes. Evidence for these two hypotheses mostly comes from studies on humans and laboratory mice. Here, we tested these hypotheses in a wild outbred population of house sparrows (
Passer domesticus
). Females were not more or less closely related to the males they paired with when considering neutral genetic variation. However, males failed to form breeding pairs when they had too few
Mhc
alleles and when they were too dissimilar from females at
Mhc
loci (i.e. had no common alleles). Furthermore, pairs did not form at random as
Mhc
diversity positively correlated in mating pairs. These results suggest that mate choice evolves in response to (i) benefits in terms of parasite resistance acquired from allelic diversity, and (ii) costs associated with the disruption of co-adapted genes.
Rapid lineage accumulation in a non-adaptive radiation: phylogenetic analysis of diversification rates in eastern North American woodland salamanders (Plethodontidae:Plethodon)
Authors: Kozak Kenneth H , Weisrock David W , Larson Allan
Published: February 2006

Adaptive radiations have served as model systems for quantifying the build-up of species richness. Few studies have quantified the tempo of diversification in species-rich clades that contain negligible adaptive disparity, making the macroevolutionary consequences of different modes of evolutionary radiation difficult to assess. We use mitochondrial-DNA sequence data and recently developed phylogenetic methodologies to explore the tempo of diversification of eastern North AmericanPlethodon, a species-rich clade of woodland salamanders exhibiting only limited phenotypic disparity. Lineage-through-time analysis reveals a high rate of lineage accumulation, 0.8 species per million years, occurring 11–8 million years ago in theP. glutinosusspecies group, followed by decreasing rates. This high rate of lineage accumulation is exceptional, comparable to the most rapid of adaptive radiations. In contrast to classic models of adaptive radiation where ecological niche divergence is linked to the origin of species, we propose that phylogenetic niche conservatism contributes to the rapid accumulation ofP. glutinosus-group lineages by promoting vicariant isolation and multiplication of species across a spatially and temporally fluctuating environment. These closely related and ecologically similar lineages persist through long-periods of evolutionary time and form strong barriers to the geographic spread of their neighbours, producing a subsequent decline in lineage accumulation. Rapid diversification among lineages exhibiting long-term maintenance of their bioclimatic niche requirements is an under-appreciated phenomenon driving the build-up of species richness.
Intercontinental community convergence of ecology and morphology in desert lizards
Authors: Melville Jane , Harmon Luke J , Losos Jonathan B
Published: February 2006

Evolutionary ecologists have long debated the extent to which communities in similar environments but different geographic regions exhibit convergence. On the one hand, if species' adaptations and community structure are determined by environmental features, convergence would be expected. However, if historical contingencies have long-lasting effects convergence would be unlikely. Most studies to date have emphasized the differences between communities in similar environments and little quantitative evidence for convergence exists. The application of comparative phylogenetic methods to ecological studies provides an opportunity to further investigate hypotheses of convergence. We compared the evolutionary patterns of structural ecology and morphology of 42 species of iguanian lizards from deserts of Australia and North America. Using a comparative approach, we found that evolutionary convergence of ecology and morphology occurs both in overall, community-wide patterns and in terms of pairs of highly similar intercontinental pairs of species. This result indicates that in these desert lizards, deterministic adaptive evolution shapes community patterns and overrides the historical contingencies unique to particular lineages.
Fossil Liposcelididae and the lice ages (Insecta: Psocodea)
Authors: Grimaldi David , Engel Michael S
Published: February 2006

Fossilized, winged adults belonging to the psocopteran family Liposcelididae are reported in amber from the mid-Cretaceous (ca100 Myr) of Myanmar (described asCretoscelis burmitica, gen. et sp. n.) and the Miocene (ca20 Myr) of the Dominican Republic (Belaphopsocus dominicussp. n.).Cretoscelisis an extinct sister group to all other Liposcelididae and the family is the free-living sister group to the true lice (order Phthiraptera, all of which are ectoparasites of birds and mammals). A phylogenetic hypothesis of relationships among genera of Liposcelididae, including fossils, reveals perfect correspondence between the chronology of fossils and cladistic rank of taxa. Lice and Liposcelididae minimally diverged 100 Myr, perhaps even in the earliest Cretaceous 145 Myr or earlier, in which case the hosts of lice would have been early mammals, early birds and possibly other feathered theropod dinosaurs, as well as haired pterosaurs.
Female freshwater crayfish adjust egg and clutch size in relation to multiple male traits
Authors: Galeotti Paolo , Rubolini Diego , Fea Gianluca , Ghia Daniela , Nardi Pietro A , Gherardi Francesca , Fasola Mauro
Published: February 2006

Females may invest more in reproduction if they acquire mates of high phenotypic quality, because offspring sired by preferred partners may be fitter than offspring sired by non-preferred ones. In this study, we tested the differential maternal allocation hypothesis in the freshwater crayfish,
Austropotamobius italicus
, by means of a pairing experiment aimed at evaluating the effects of specific male traits (body size, chelae size and chelae asymmetry) on female primary reproductive effort. Our results showed that females laid larger but fewer eggs for relatively small-sized, large-clawed males, and smaller but more numerous eggs for relatively large-sized, small-clawed males. Chelae asymmetry had no effects on female reproductive investment. While the ultimate consequences of this pattern of female allocation remain unclear, females were nevertheless able to adjust their primary reproductive effort in relation to mate characteristics in a species where inter-male competition and sexual coercion may mask or obscure their sexual preferences. In addition, our results suggest that female allocation may differentially affect male characters, thus promoting a trade-off between the expression of different male traits.
Age-dependent diet choice in an avian top predator
Authors: Rutz Christian , Whittingham Mark J , Newton Ian
Published: February 2006

Age-dependent breeding performance is arguably one of the best-documented phenomena in ornithology. The existence of age-related trends has major implications for life-history theory, but the proximate reasons for these patterns remain poorly understood. It has been proposed that poor breeding performance of young individuals might reflect lack of foraging skills. We investigated this possibility in a medium-sized, powerful raptor—the northern goshawkAccipiter gentilis. Male goshawks are responsible for providing their females and their offspring with food. We hypothesized that young males may generally show poor breeding performance or even delay breeding, because they lack the experience to hunt efficiently—especially, their principal avian prey, the feral pigeonColumba livia. Our study exploited a rare ‘natural experiment’, the expansion phase of an urban population, where intraspecific interference was negligible and many young males bred successfully. This enabled us to examine the improvement of foraging skills in a larger sample of young individuals, and in more controlled conditions than usually possible. Using data from individually identified male breeders, we show that, consistent with our hypothesis, the proportion of pigeons in the diet increased significantly with male age, for at least the first three years of life. Other studies have shown a parallel increase in productivity, and a positive effect of a pigeon-rich diet on brood size and nestling condition, stressing the potential fitness relevance of this prey species for goshawks. Our results suggest a causal link between patterns of age-dependence in foraging ecology and reproductive performance. Furthermore, our study is, to our knowledge, the first demonstration that prey choice of breeders, which might reflect individual hunting skills, is age-dependent in a raptor.
Estimating individual contributions to population growth: evolutionary fitness in ecological time
Authors: Coulson T , Benton T.G , Lundberg P , Dall S.R.X , Kendall B.E , Gaillard J.-M
Published: February 2006

Ecological and evolutionary change is generated by variation in individual performance. Biologists have consequently long been interested in decomposing change measured at the population level into contributions from individuals, the traits they express and the alleles they carry. We present a novel method of estimating individual contributions to population growth and changes in distributions of quantitative traits and alleles. An individual's contribution to population growth is an individual's realized annual fitness. We demonstrate how the quantities we develop can be used to address a range of empirical questions, and provide an application to a detailed dataset of Soay sheep. The approach provides results that are consistent with those obtained using lifetime estimates of individual performance, yet is substantially more powerful as it allows lifetime performance to be decomposed into annual survival and fecundity contributions.
The ties that bind: genetic relatedness predicts the fission and fusion of social groups in wild African elephants
Authors: Archie Elizabeth A , Moss Cynthia J , Alberts Susan C
Published: February 2006

Many social animals live in stable groups. In contrast, African savannah elephants (Loxodonta africana) live in unusually fluid, fission–fusion societies. That is, ‘core’ social groups are composed of predictable sets of individuals; however, over the course of hours or days, these groups may temporarily divide and reunite, or they may fuse with other social groups to form much larger social units. Here, we test the hypothesis that genetic relatedness predicts patterns of group fission and fusion among wild, female African elephants. Our study of a single Kenyan population spans 236 individuals in 45 core social groups, genotyped at 11 microsatellite and one mitochondrial DNA (mtDNA) locus. We found that genetic relatedness predicted group fission; adult females remained with their first order maternal relatives when core groups fissioned temporarily. Relatedness also predicted temporary fusion between social groups; core groups were more likely to fuse with each other when the oldest females in each group were genetic relatives. Groups that shared mtDNA haplotypes were also significantly more likely to fuse than groups that did not share mtDNA. Our results suggest that associations between core social groups persist for decades after the original maternal kin have died. We discuss these results in the context of kin selection and its possible role in the evolution of elephant sociality.
Cascading host-associated genetic differentiation in parasitoids of phytophagous insects
Authors: Stireman John O , Nason John D , Heard Stephen B , Seehawer Julie M
Published: February 2006

The extraordinary diversity of phytophagous insects may be attributable to their narrow specialization as parasites of plants, with selective tradeoffs associated with alternate host plants driving genetic divergence of host-associated forms via ecological speciation. Most phytophagous insects in turn are attacked by parasitoid insects, which are similarly specialized and may also undergo host-associated differentiation (HAD). A particularly interesting possibility is that HAD by phytophagous insects might lead to HAD in parasitoids, as parasitoids evolve divergent lineages on the new host plant-specific lineages of their phytophagous hosts. We call this process ‘cascading host-associated differentiation’ (cascading HAD). We tested for cascading HAD in parasitoids of two phytophagous insects, each of which consists of genetically distinct host-associated lineages on the same pair of goldenrods (Solidago). Each parasitoid exhibited significant host-associated genetic divergence, and the distribution and patterns of divergence are consistent with divergence in sympatry. Although evidence for cascading HAD is currently limited, our results suggest that it could play an important role in the diversification of parasitoids attacking phytophagous insects. The existence of cryptic host-associated lineages also suggests that the diversity of parasitoids may be vastly underestimated.
Automated biometrics-based personal identification of the Hunter–Schreger bands of dental enamel
Authors: Ramenzoni Liza L , Line Sérgio R.P
Published: February 2006

The use of automated biometrics-based personal identification systems is a ubiquitous procedure in present times. Biometrics has certain limitations, such as in cases when bodies are decomposed, burned, or only small fragments of calcified tissues remain. Dental enamel is the most mineralized tissue of organisms and resists post-mortem degradation. It is characterized by layers of prisms of regularly alternating directions, known as Hunter–Schreger bands (HSB). In this article, we show that the pattern variation of the HSB, referred here as toothprint, can be used as a biometric-based parameter for personal identification in automated systems.
Quantifying lymphocyte kinetics
in vivo
using carboxyfluorescein diacetate succinimidyl ester
Authors: Asquith Becca , Debacq Christophe , Florins Arnaud , Gillet Nicolas , Sanchez-Alcaraz Teresa , Mosley Angelina , Willems Luc
Published: February 2006

The cytoplasmic dye carboxyfluorescein diacetate succinimidyl ester (CFSE) is used to quantify cell kinetics. It is particularly important in studies of lymphocyte homeostasis where its labelling of cells irrespective of their stage in the cell cycle makes it preferable to deuterated glucose and BrdU which only label dividing cells and thus produce unrepresentative results. In the past, experiments have been limited by the need to obtain a clear separation of CFSE peaks forcing scientists to adopt a strategy of
in vitro
labelling of cells followed by their injection into the host. Here we develop a framework for analysis of
in vivo
CFSE labelling data. This enables us to estimate the rate of proliferation and death of lymphocytes
in situ
, and thus represents a considerable advance over current procedures. We illustrate this approach using
in vivo
CFSE labelling of B lymphocytes in sheep.
The predation costs of symmetrical cryptic coloration
Authors: Cuthill Innes C , Hiby Elly , Lloyd Emily
Published: February 2006

In psychological studies of visual perception, symmetry is accepted as a potent cue in visual search for cryptic objects, yet its importance for non-human animals has been assumed rather than tested. Furthermore, while the salience of bilateral symmetry has been established in laboratory-based search tasks using human subjects, its role in more natural settings, closer to those for which such perceptual mechanisms evolved, has not, to our knowledge, been investigated previously. That said, the salience of symmetry in visual search has a plausible adaptive rationale, because biologically important objects, such as prey, predators or conspecifics, usually have a plane of symmetry that is not present in their surroundings. We tested the conspicuousness to avian predators of cryptic artificial, moth-like targets, with or without bilateral symmetry in background-matching coloration, against oak trees in the field. In two independent experiments, symmetrical targets were predated at a higher rate than otherwise identical asymmetrical targets. There was a small, but significant, fitness cost to symmetry in camouflage patterns. Given that birds are the most commonly invoked predators shaping the evolution of defensive coloration in insects, this raises the question of why bilateral asymmetry is not more common in cryptic insects.
Alien mink predation induces prolonged declines in archipelago amphibians
Authors: Ahola Markus , Nordström Mikael , Banks Peter B , Laanetu Nikolai , Korpimäki Erkki
Published: February 2006

Amphibians are undergoing enigmatic global declines variously attributed to a complex web of anthropogenic forces. Alien predators pose a fundamental threat to biodiversity generally that is predicted to be most acute in island ecosystems. While amphibian eggs and tadpoles are vulnerable to aquatic predators, the effect of predators on adult, reproducing frogs, which most influence amphibian population processes, is unknown. Here, we report on the responses of amphibian populations in the outer Finnish Archipelago to a long-term, large-scale removal of American mink (
Mustela vison
Schreb.), an invasive predator linked to recent biodiversity loss across Europe. Removal increased both the densities and distribution of common frogs (
Rana temporaria
L.) but not those of common toads (
Bufo bufo
L.), which appear to escape mink predation because of their unpalatable skin. Importantly, the largest benefits of mink removal to frog recovery were slow to appear as frogs apparently have a delayed maturation in these harsh environments, which means we must be cautious about reliance upon short-term results.
Coordination and communication between the p53 and IGF-1–AKT–TOR signal transduction pathways
Authors: Levine Arnold J. , Feng Zhaohui , Mak Tak W. , You Han , Jin Shengkan
Published: February 2006

Over the past 10 years the signal transduction networks for p53, IGF-1-AKT, and TOR pathways have been assembled in worms, flies, and mammals, and their functions elucidated. In the past 1-2 years a number of genes and their proteins have been identified that permit extensive communication and coordination between these pathways. These three pathways are involved in sensing and integrating signals arising from nutrient and growth factor availability, signals from sensory and sexual organs, and intrinsic and extrinsic stress signals. In turn these pathways regulate cell growth, proliferation, and death. These networks are central to our understanding of a variety of physiological and pathological conditions, including cancer, diabetes, and longevity.
Control of ribonucleotide reductase localization through an anchoring mechanism involving Wtm1
Authors: Lee Yang David , Elledge Stephen J.
Published: February 2006

The control of deoxyribonucleotide levels is essential for DNA synthesis and repair. This control is exerted through regulation of ribonucleotide reductase (RNR). One mode of RNR regulation is differential localization of its subunits. In Saccharomyces cerevisiae, the catalytic subunit hererodimer, Rnr2/Rnr4, is localized to the nucleus while its regulatory subunit, Rnr1, is cytoplasmic. During S phase and in response to DNA damage, Rnr2-Rnr4 enters the cytoplasm, where it presumably combines with Rnr1 to form an active complex. The mechanism of its nuclear localization is not understood. Here, we report the isolation of the WTM (WD40-containing transcriptional modulator) proteins as regulators of Rnr2/Rnr4 localization. Overproduction of Wtm2 increased Rnr2/Rnr4. Deletion of WTM1, a homolog of WTM2, leads to the cytoplasmic localization of Rnr2/Rnr4, and increased hydroxyurea (HU)-resistance in mec1 mutants. Wtm1 binds Rnr2/4 complexes and release them to the cytoplasm in response to DNA damage. Forced localization of Wtm1 to the nucleolus causes Rnr2/Rnr4 complexes to relocalize to the nucleolus. Thus, Wtm1 acts as a nuclear anchor to maintain nuclear localization of Rnr2/4 complexes outside of S phase. In the presence of DNA damage this association is disrupted and Rnr2/Rnr4 become cytoplasmic, where they join with Rnr1 to form an intact complex.
Selective and antagonistic functions of SWI/SNF and Mi-2β nucleosome remodeling complexes during an inflammatory response
Authors: Ramirez-Carrozzi Vladimir R. , Nazarian Aaron A. , Li Caiyi C. , Gore Sarah L. , Sridharan Rupa , Imbalzano Anthony N. , Smale Stephen T.
Published: February 2006

Studies of mammalian genes activated in response to an acute stimulus have suggested diverse mechanisms through which chromatin structure and nucleosome remodeling events contribute to inducible gene transcription. However, because of this diversity, the logical organization of the genome with respect to nucleosome remodeling and gene induction has remained obscure. Numerous proinflammatory genes are rapidly induced in macrophages in response to microbial infection. Here, we show that in lipopolysaccharide-stimulated macrophages, the catalytic BRG1/BRM subunits of the SWI/SNF class of ATP-dependent nucleosome remodeling complexes are consistently required for the activation of secondary response genes and primary response genes induced with delayed kinetics, but not for rapidly induced primary response genes. Surprisingly, a Mi-2β complex was selectively recruited along with the SWI/SNF complexes to the control regions of secondary response and delayed primary response genes, with the Mi-2β complex acting antagonistically to limit the induction of these gene classes. SWI/SNF and Mi-2β complexes influenced cell size in a similarly antagonistic manner. These results provide insight into the differential contributions of nucleosome remodeling complexes to the rapid induction of defined classes of mammalian genes and reveal a robust anti-inflammatory function of Mi-2β.
Critical and distinct roles for key RET tyrosine docking sites in renal development
Authors: Jain Sanjay , Encinas Mario , Johnson Eugene M. , Milbrandt Jeffrey
Published: February 2006

Molecular mechanisms that lead to congenital anomalies of kidneys and the lower urinary tract (CAKUT) are poorly understood. To elucidate the molecular basis for signaling specificity of GDNF-mediated RET signaling in kidney development, we characterized mice that exclusively express either the human RET9 or RET51 isoform, or express these isoforms with individual mutations in docking tyrosines for PTB and SH2-domain-containing adaptors Src (Y981), PLCγ (Y1015), and Shc (Y1062). Our results provide evidence for differential and isoform-specific roles of these docking sites in murine kidney development. Homozygous RetRET9 and RetRET51 mice were viable and show normally developed kidneys, indicating redundant roles of human RET isoforms in murine kidney development. In the context of the RET51 isoform, only mutation of the docking Tyr 1015 (Y1015F) resulted in severe renal anomalies. These included bilateral megaureters and multicystic kidneys that were caused by supernumerary ureteric buds that fail to separate from the wolffian duct as well as decreased branching morphogenesis. Similar kidney and ureter defects were observed in RET9(Y1015F) mice that contain the Y1015F mutation in the RET9 isoform. Interestingly, loss of RET9(Y1062)-mediated AKT/MAPK activation resulted in renal agenesis or kidney rudiments, whereas mutation of this residue in RET51 had no obvious effect on AKT/MAPK activity and renal development. These results reveal novel roles of key RET-dependent signaling pathways in embryonic kidney development and provide murine models and new insights into the molecular basis for CAKUT.
Target hub proteins serve as master regulators of development in yeast
Authors: Borneman Anthony R. , Leigh-Bell Justine A. , Yu Haiyuan , Bertone Paul , Gerstein Mark , Snyder Michael
Published: February 2006

To understand the organization of the transcriptional networks that govern cell differentiation, we have investigated the transcriptional circuitry controlling pseudohyphal development inSaccharomyces cerevisiae. The binding targets of Ste12, Tec1, Sok2, Phd1, Mga1, and Flo8 were globally mapped across the yeast genome. The factors and their targets form a complex binding network, containing patterns characteristic of autoregulation, feedback and feed-forward loops, and cross-talk. Combinatorial binding to intergenic regions was commonly observed, which allowed for the identification of a novel binding association between Mga1 and Flo8, in which Mga1 requires Flo8 for binding to promoter regions. Further analysis of the network showed that the promoters ofMGA1andPHD1were bound by all of the factors used in this study, identifying them as key target hubs. Overexpression of either of these two proteins specifically induced pseudohyphal growth under noninducing conditions, highlighting them as master regulators of the system. Our results indicate that target hubs can serve as master regulators whose activity is sufficient for the induction of complex developmental responses and therefore represent important regulatory nodes in biological networks.
A mechanism of AP-1 suppression through interaction of c-Fos with lamin A/C
Authors: Ivorra Carmen , Kubicek Markus , González José M. , Sanz-González Silvia M. , Álvarez-Barrientos Alberto , O'Connor José-Enrique , Burke Brian , Andrés Vicente
Published: February 2006

AP-1 (Activating Protein 1) transcription factor activity is tightly regulated at multiple levels, including dimer formation (i.e., Fos/Jun). Here we show that the intermediate filament protein lamin A/C suppresses AP-1 function through direct interaction with c-Fos, and that both proteins can interact and colocalize at the nuclear envelope (NE) in mammalian cells. Perinuclear localization of c-Fos is absent in Lmna-null cells but can be restored by lamin A overexpression. In vitro, preincubation of c-Fos with lamin A prior to the addition of c-Jun inhibits AP-1 DNA-binding activity. In vivo, overexpression of lamin A reduces the formation of c-Fos/c-Jun heterodimers, and suppresses AP-1 DNA-binding and transcriptional activity. Notably, c-Fos colocalizes with lamin A/C at the NE in starvation-synchronized quiescent cells lacking detectable AP-1 DNA binding. In contrast, serum-induced AP-1 DNA-binding activity coincides with abundant nucleoplasmic c-Fos expression without changes in lamin A/C localization. We also found that Lmna-null cells display enhanced proliferation. In contrast, lamin A overexpression causes growth arrest, and ectopic c-Fos partially overcomes lamin A/C-induced cell cycle alterations. We propose lamin A/C-mediated c-Fos sequestration at the NE as a novel mechanism of transcriptional and cell cycle control.
Mammalian sperm translate nuclear-encoded proteins by mitochondrial-type ribosomes
Authors: Gur Yael , Breitbart Haim
Published: February 2006

It is widely accepted that spermatozoa are translationally silent. The present study demonstrates, for the first time, incorporation of labeled amino acids into polypeptides during sperm capacitation, which was completely inhibited by mitochondrial translation inhibitors but not by the cytoplasmic translation inhibitor. Unlike 80S cytoplasmic ribosomes, 55S mitochondrial ribosomes were present in polysomal fractions, indicating that these ribosomes are actively involved in protein translation in spermatozoa. Inhibition of protein translation significantly reduced sperm motility, capacitation and in vitro fertilization rate. Thus, contrary to the accepted dogma, nuclear genes are expressed as proteins in sperm during their residence in the female reproductive tract until fertilization.
Telomere elongation is under the control of the RNAi-based mechanism in the Drosophila germline
Authors: Savitsky Mikhail , Kwon Dmitry , Georgiev Pavel , Kalmykova Alla , Gvozdev Vladimir
Published: February 2006

Telomeres in Drosophila are maintained by transposition of specialized telomeric retroelements HeT-A, TAHRE, and TART instead of the short DNA repeats generated by telomerase in other eukaryotes. Here we implicate the RNA interference machinery in the control of Drosophila telomere length in ovaries. The abundance of telomeric retroelement transcripts is up-regulated owing to mutations in the spn-E and aub genes, encoding a putative RNA helicase and protein of the Argonaute family, respectively, which are related to the RNA interference (RNAi) machinery. These mutations cause an increase in the frequency of telomeric element retrotransposition to a broken chromosome end. spn-E mutations eliminate HeT-A and TART short RNAs in ovaries, suggesting an RNAi-based mechanism in the control of telomere maintenance in the Drosophila germline. Enhanced frequency of TART, but not HeT-A, attachments in individuals carrying one dose of mutant spn-E or aub alleles suggests that TART is a primary target of the RNAi machinery. At the same time, we detected enhanced HeT-A attachments to broken chromosome ends in oocytes from homozygous spn-E mutants. Double-stranded RNA (dsRNA)-mediated control of telomeric retroelement transposition may occur at premeiotic stages, resulting in the maintenance of appropriate telomere length in gamete precursors.
Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3′ UTR: translational repression for dosage compensation
Authors: Duncan Kent , Grskovic Marica , Strein Claudia , Beckmann Karsten , Niggeweg Ricarda , Abaza Irina , Gebauer Fátima , Wilm Matthias , Hentze Matthias W.
Published: February 2006

MSL-2 (male-specific lethal 2) is the limiting component of the Drosophila dosage compensation complex (DCC) that specifically increases transcription from the male X chromosome. Ectopic expression of MSL-2 protein in females causes DCC assembly on both X chromosomes and lethality. Inhibition of MSL-2 synthesis requires the female-specific protein sex-lethal (SXL), which binds to the msl-2 mRNA 5′ and 3′ untranslated regions (UTRs) and blocks translation through distinct UTR-specific mechanisms. Here, we purify translationally silenced msl-2 mRNPs and identify UNR (upstream of N-ras) as a protein recruited to the 3′ UTR by SXL. We demonstrate that SXL requires UNR as a corepressor for 3′-UTR-mediated regulation, imparting a female-specific function to the ubiquitously expressed UNR protein. Our results reveal a novel functional role for UNR as a translational repressor and indicate that UNR is a key component of a “fail-safe” dosage compensation regulatory system that prevents toxic MSL-2 synthesis in female cells.
Drosophila UNR is required for translational repression of male-specific lethal 2 mRNA during regulation of X-chromosome dosage compensation
Authors: Abaza Irina , Coll Olga , Patalano Solenn , Gebauer Fátima
Published: February 2006

The inhibition of male-specific lethal 2 (msl-2) mRNA translation by the RNA-binding protein sex-lethal (SXL) is an essential regulatory step for X-chromosome dosage compensation in Drosophila melanogaster. The mammalian upstream of N-ras (UNR) protein has been implicated in the regulation of mRNA stability and internal ribosome entry site (IRES)-dependent mRNA translation. Here we have identified the Drosophila homolog of mammalian UNR as a cofactor required for SXL-mediated repression of msl-2 translation. UNR interacts with SXL, a female-specific protein. Although UNR is present in both male and female flies, binding of SXL to uridine-rich sequences in the 3′ untranslated region (UTR) of msl-2 mRNA recruits UNR to adjacent regulatory sequences, thereby conferring a sex-specific function to UNR. These data identify a novel regulator of dosage compensation in Drosophila that acts coordinately with SXL in translational control.
A systematic model to predict transcriptional regulatory mechanisms based on overrepresentation of transcription factor binding profiles
Authors: Chang Li-Wei , Nagarajan Rakesh , Magee Jeffrey A. , Milbrandt Jeffrey , Stormo Gary D.
Published: February 2006

An important aspect of understanding a biological pathway is to delineate the transcriptional regulatory mechanisms of the genes involved. Two important tasks are often encountered when studying transcription regulation, i.e., (1) the identification of common transcriptional regulators of a set of coexpressed genes; (2) the identification of genes that are regulated by one or several transcription factors. In this study, a systematic and statistical approach was taken to accomplish these tasks by establishing an integrated model considering all of the promoters and characterized transcription factors (TFs) in the genome. A promoter analysis pipeline (PAP) was developed to implement this approach. PAP was tested using coregulated gene clusters collected from the literature. In most test cases, PAP identified the transcription regulators of the input genes accurately. When compared with chromatin immunoprecipitation experiment data, PAP's predictions are consistent with the experimental observations. When PAP was used to analyze one published expression-profiling data set and two novel coregulated gene sets, PAP was able to generate biologically meaningful hypotheses. Therefore, by taking a systematic approach of considering all promoters and characterized TFs in our model, we were able to make more reliable predictions about the regulation of gene expression in mammalian organisms.